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PMC:2664230 / 172-5223 JSONTXT

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bionlp-st-ge-2016-reference

Id Subject Object Predicate Lexical cue Negation Speculation
T64 411-417 Regulation denotes alters
T65 418-423 Protein denotes TNF-α
T66 424-434 Gene_expression denotes production
T67 435-453 Positive_regulation denotes in the presence of
T68 667-681 Phosphorylation denotes phosphorylated
T69 694-699 Protein denotes I-κBα
T70 719-722 Protein denotes p65
T71 888-893 Protein denotes TNF-α
T72 1108-1114 Negative_regulation denotes reduce
T73 1108-1114 Negative_regulation denotes reduce
T74 1127-1132 Protein denotes I-κBα
T75 1133-1148 Phosphorylation denotes phosphorylation
T76 1158-1161 Protein denotes p65
T77 1162-1177 Phosphorylation denotes phosphorylation
T78 1352-1360 Localization denotes secreted
T79 1379-1384 Protein denotes TNF-α
T80 1392-1400 Regulation denotes presence
T81 1405-1412 Regulation denotes absence true
T1133 2575-2585 Negative_regulation denotes attenuated
T1134 2780-2784 Positive_regulation denotes lead
T1135 2792-2806 Negative_regulation denotes downregulation
T1136 2810-2815 Protein denotes TNF-α
T1137 2816-2826 Gene_expression denotes production
T1138 3854-3861 Negative_regulation denotes inhibit
T1139 3868-3877 Regulation denotes dependent
T1140 3900-3913 Transcription denotes transcription
T1141 3935-3940 Protein denotes TNF-α
T1142 4024-4038 Negative_regulation denotes down-regulates
T1143 4039-4044 Protein denotes TNF-α
T1144 4045-4055 Gene_expression denotes production
T1145 4703-4707 Regulation denotes role true
T1146 4722-4729 Positive_regulation denotes induced
T1147 4730-4735 Protein denotes TNF-α
T1148 4736-4746 Gene_expression denotes production
T57 32-38 Regulation denotes effect true
T58 122-149 Protein denotes tumor necrosis factor-alpha
T59 151-156 Protein denotes TNF-α
T60 158-168 Gene_expression denotes production
T61 251-261 Gene_expression denotes production
T62 265-270 Protein denotes TNF-α
T63 271-280 Positive_regulation denotes following
T1126 2386-2395 Regulation denotes regulator
T1127 2399-2422 Protein denotes tumor necrosis factor-α
T1128 2424-2429 Protein denotes TNF-α
T1129 2431-2441 Gene_expression denotes production
T1130 2444-2449 Protein denotes TNF-α
T1131 2552-2557 Protein denotes TNF-α
T1132 2558-2567 Gene_expression denotes synthesis
R33 T64 T67 themeOf alters,in the presence of
R34 T65 T66 themeOf TNF-α,production
R35 T66 T64 themeOf production,alters
R36 T69 T68 themeOf I-κBα,phosphorylated
R37 T74 T75 themeOf I-κBα,phosphorylation
R38 T75 T73 themeOf phosphorylation,reduce
R39 T76 T77 themeOf p65,phosphorylation
R40 T77 T72 themeOf phosphorylation,reduce
R41 T78 T80 themeOf secreted,presence
R42 T78 T81 themeOf secreted,absence
R43 T79 T78 themeOf TNF-α,secreted
R750 T58 T60 themeOf tumor necrosis factor-alpha,production
R751 T60 T57 themeOf production,effect
R752 T61 T63 themeOf production,following
R753 T62 T61 themeOf TNF-α,production
R832 T1127 T1129 themeOf tumor necrosis factor-α,production
R833 T1128 T1127 equivalentTo TNF-α,tumor necrosis factor-α
R834 T1129 T1126 themeOf production,regulator
R835 T1131 T1132 themeOf TNF-α,synthesis
R836 T1132 T1133 themeOf synthesis,attenuated
R837 T1135 T1134 themeOf downregulation,lead
R838 T1136 T1137 themeOf TNF-α,production
R839 T1137 T1135 themeOf production,downregulation
R840 T1139 T1138 themeOf dependent,inhibit
R841 T1140 T1139 themeOf transcription,dependent
R842 T1141 T1140 themeOf TNF-α,transcription
R843 T1143 T1144 themeOf TNF-α,production
R844 T1144 T1142 themeOf production,down-regulates
R845 T1146 T1145 themeOf induced,role
R846 T1147 T1148 themeOf TNF-α,production
R847 T1148 T1146 themeOf production,induced

2_test

Id Subject Object Predicate Lexical cue
18568240-12168567-22101112 2313-2314 12168567 denotes 2
18568240-9442376-22101113 2442-2443 9442376 denotes 3
18568240-2460096-22101114 2708-2709 2460096 denotes 4
18568240-1847694-22101115 3102-3103 1847694 denotes 5
18568240-12829247-22101116 3321-3322 12829247 denotes 6
18568240-12829247-22101117 3637-3638 12829247 denotes 6
18568240-15044179-22101117 3637-3638 15044179 denotes 6
18568240-15221855-22101117 3637-3638 15221855 denotes 6
18568240-8702838-22101118 3946-3947 8702838 denotes 9

pmc-enju-pas

Id Subject Object Predicate Lexical cue
T473 0-4 DT denotes this
T474 5-10 NN denotes study
T475 11-14 VB denotes was
T476 15-17 TO denotes to
T477 18-27 VB denotes determine
T478 28-31 DT denotes the
T479 32-38 NN denotes effect
T480 39-41 IN denotes of
T481 42-53 JJ denotes nonspecific
T482 54-71 NN denotes phosphodiesterase
T483 72-82 NN denotes inhibition
T484 83-85 IN denotes on
T485 86-99 NN denotes transcription
T486 100-106 NN denotes factor
T487 107-117 NN denotes activation
T488 118-121 CC denotes and
T489 122-127 NN denotes tumor
T490 128-136 NN denotes necrosis
T491 137-149 NN denotes factor-alpha
T492 150-151 -LRB- denotes (
T493 151-156 NN denotes TNF-α
T494 156-157 -RRB- denotes )
T495 158-168 NN denotes production
T496 169-171 IN denotes in
T497 172-190 NN denotes lipopolysaccharide
T498 191-192 -LRB- denotes (
T499 192-195 NN denotes LPS
T500 195-196 -RRB- denotes )
T501 196-207 JJ denotes -stimulated
T502 208-213 JJ denotes human
T503 214-225 JJ denotes mononuclear
T504 226-231 NN denotes cells
T505 234-246 NN denotes INTRODUCTION
T506 247-250 DT denotes The
T507 251-261 NN denotes production
T508 262-264 IN denotes of
T509 265-270 NN denotes TNF-α
T510 271-280 VB denotes following
T511 281-284 NN denotes LPS
T512 285-296 NN denotes stimulation
T513 297-299 VB denotes is
T514 300-303 CD denotes one
T515 304-306 IN denotes of
T516 307-310 DT denotes the
T517 311-314 JJ denotes key
T518 315-320 NN denotes steps
T519 321-323 IN denotes in
T520 324-333 JJ denotes bacterial
T521 334-340 NN denotes sepsis
T522 341-344 CC denotes and
T523 345-357 NN denotes inflammation
T524 359-362 DT denotes The
T525 363-372 NN denotes mechanism
T526 373-375 IN denotes by
T527 376-381 WDT denotes which
T528 382-399 NN denotes phosphodiesterase
T529 400-410 NN denotes inhibition
T530 411-417 VB denotes alters
T531 418-423 NN denotes TNF-α
T532 424-434 NN denotes production
T533 435-437 IN denotes in
T534 438-441 DT denotes the
T535 442-450 NN denotes presence
T536 451-453 IN denotes of
T537 454-457 NN denotes LPS
T538 458-465 VB denotes remains
T539 466-473 JJ denotes unclear
T540 476-483 NN denotes METHODS
T541 484-489 JJ denotes Human
T542 490-501 JJ denotes mononuclear
T543 502-507 NN denotes cells
T544 508-512 VB denotes were
T545 513-523 VB denotes stimulated
T546 524-528 IN denotes with
T547 529-532 NN denotes LPS
T548 533-534 -LRB- denotes (
T549 534-535 CD denotes 1
T550 536-541 NN denotes μg/mL
T551 541-542 -RRB- denotes )
T552 542-543 -COMMA- denotes ,
T553 544-546 IN denotes in
T554 547-550 DT denotes the
T555 551-559 NN denotes presence
T556 560-563 CC denotes and
T557 564-571 NN denotes absence
T558 572-574 IN denotes of
T559 575-589 NN denotes Pentoxifylline
T560 590-591 -LRB- denotes (
T561 591-594 NN denotes PTX
T562 594-595 -COLON- denotes ;
T563 596-598 CD denotes 20
T564 599-601 NN denotes mM
T565 601-602 -RRB- denotes )
T566 602-603 -COMMA- denotes ,
T567 604-605 DT denotes a
T568 606-617 JJ denotes nonspecific
T569 618-635 NN denotes phosphodiesterase
T570 636-645 NN denotes inhibitor
T571 647-654 JJ denotes Western
T572 655-663 NN denotes blotting
T573 664-666 IN denotes of
T574 667-681 VB denotes phosphorylated
T575 682-693 JJ denotes cytoplasmic
T576 694-699 NN denotes I-κBα
T577 699-700 -COMMA- denotes ,
T578 701-708 JJ denotes nuclear
T579 709-718 NN denotes factor-κB
T580 719-722 NN denotes p65
T581 723-724 -LRB- denotes (
T582 724-729 NN denotes NF-κB
T583 729-730 -RRB- denotes )
T584 730-731 -COMMA- denotes ,
T585 732-735 CC denotes and
T586 736-743 JJ denotes nuclear
T587 744-757 JJ denotes cAMP-response
T588 758-765 NN denotes element
T589 766-773 NN denotes binding
T590 774-781 NN denotes protein
T591 782-783 -LRB- denotes (
T592 783-787 NN denotes CREB
T593 787-788 -RRB- denotes )
T594 789-792 VB denotes was
T595 793-802 VB denotes performed
T596 804-807 NN denotes DNA
T597 808-815 NN denotes binding
T598 816-818 IN denotes of
T599 819-824 NN denotes NF-κB
T600 825-828 CC denotes and
T601 829-833 NN denotes CREB
T602 834-837 VB denotes was
T603 838-846 VB denotes verified
T604 847-849 IN denotes by
T605 850-865 JJ denotes electrophoretic
T606 866-874 NN denotes mobility
T607 875-880 NN denotes shift
T608 881-886 NN denotes assay
T609 888-893 NN denotes TNF-α
T610 894-900 NN denotes levels
T611 901-905 VB denotes were
T612 906-916 VB denotes determined
T613 917-919 IN denotes in
T614 920-923 DT denotes the
T615 924-935 NN denotes supernatant
T616 936-938 IN denotes of
T617 939-949 VB denotes stimulated
T618 950-955 NN denotes cells
T619 956-958 IN denotes in
T620 959-962 DT denotes the
T621 963-971 NN denotes presence
T622 972-975 CC denotes and
T623 976-983 NN denotes absence
T624 984-991 NN denotes Protein
T625 992-998 NN denotes kinase
T626 999-1000 NN denotes A
T627 1001-1011 NN denotes inhibition
T628 1012-1014 IN denotes by
T629 1015-1017 DT denotes an
T630 1018-1031 JJ denotes enzyme-linked
T631 1032-1045 JJ denotes immunosorbent
T632 1046-1051 NN denotes assay
T633 1052-1053 -LRB- denotes (
T634 1053-1058 NN denotes ELISA
T635 1058-1059 -RRB- denotes )
T636 1062-1069 NN denotes RESULTS
T637 1070-1073 NN denotes PTX
T638 1074-1077 VB denotes was
T639 1078-1090 VB denotes demonstrated
T640 1091-1093 TO denotes to
T641 1094-1107 RB denotes significantly
T642 1108-1114 VB denotes reduce
T643 1115-1126 JJ denotes cytoplasmic
T644 1127-1132 NN denotes I-κBα
T645 1133-1148 NN denotes phosphorylation
T646 1148-1149 -COMMA- denotes ,
T647 1150-1157 JJ denotes nuclear
T648 1158-1161 NN denotes p65
T649 1162-1177 NN denotes phosphorylation
T650 1177-1178 -COMMA- denotes ,
T651 1179-1182 CC denotes and
T652 1183-1186 DT denotes the
T653 1187-1190 NN denotes DNA
T654 1191-1198 NN denotes binding
T655 1199-1207 NN denotes activity
T656 1208-1210 IN denotes of
T657 1211-1216 NN denotes NF-κB
T658 1218-1220 IN denotes In
T659 1221-1229 NN denotes contrast
T660 1229-1230 -COMMA- denotes ,
T661 1231-1234 NN denotes PTX
T662 1235-1243 RB denotes markedly
T663 1244-1252 VB denotes enhanced
T664 1253-1256 DT denotes the
T665 1257-1272 NN denotes phosphorylation
T666 1273-1276 CC denotes and
T667 1277-1280 NN denotes DNA
T668 1281-1288 NN denotes binding
T669 1289-1297 NN denotes activity
T670 1298-1300 IN denotes of
T671 1301-1305 NN denotes CREB
T672 1307-1312 NN denotes Cells
T673 1313-1326 RB denotes concomitantly
T674 1327-1334 VB denotes treated
T675 1335-1339 IN denotes with
T676 1340-1343 NN denotes PTX
T677 1344-1347 CC denotes and
T678 1348-1351 NN denotes LPS
T679 1352-1360 VB denotes secreted
T680 1361-1368 JJ denotes similar
T681 1369-1375 NN denotes levels
T682 1376-1378 IN denotes of
T683 1379-1384 NN denotes TNF-α
T684 1385-1387 IN denotes in
T685 1388-1391 DT denotes the
T686 1392-1400 NN denotes presence
T687 1401-1404 CC denotes and
T688 1405-1412 NN denotes absence
T689 1413-1420 NN denotes Protein
T690 1421-1427 NN denotes kinase
T691 1428-1429 NN denotes A
T692 1430-1440 NN denotes inhibition
T693 1443-1453 NN denotes DISCUSSION
T694 1454-1457 DT denotes The
T695 1458-1467 VB denotes increased
T696 1468-1473 NN denotes level
T697 1474-1476 IN denotes of
T698 1477-1481 NN denotes cAMP
T699 1482-1486 WDT denotes that
T700 1487-1494 VB denotes results
T701 1495-1499 IN denotes from
T702 1500-1517 NN denotes phosphodiesterase
T703 1518-1528 NN denotes inhibition
T704 1529-1536 VB denotes affects
T705 1537-1548 JJ denotes cytoplasmic
T706 1549-1552 CC denotes and
T707 1553-1560 JJ denotes nuclear
T708 1561-1567 NN denotes events
T709 1567-1568 -COMMA- denotes ,
T710 1569-1578 VB denotes resulting
T711 1579-1581 IN denotes in
T712 1582-1585 DT denotes the
T713 1586-1597 NN denotes attenuation
T714 1598-1600 IN denotes of
T715 1601-1606 NN denotes NF-κB
T716 1607-1610 CC denotes and
T717 1611-1614 DT denotes the
T718 1615-1625 NN denotes activation
T719 1626-1628 IN denotes of
T720 1629-1633 NN denotes CREB
T721 1634-1649 JJ denotes transcriptional
T722 1650-1653 NN denotes DNA
T723 1654-1661 NN denotes binding
T724 1662-1669 IN denotes through
T725 1670-1678 NN denotes pathways
T726 1679-1683 WDT denotes that
T727 1684-1687 VB denotes are
T728 1688-1697 RB denotes partially
T729 1698-1705 NN denotes Protein
T730 1706-1712 NN denotes kinase
T731 1713-1726 JJ denotes A-independent
T732 1729-1739 NN denotes CONCLUSION
T733 1740-1752 JJ denotes PTX-mediated
T734 1753-1770 NN denotes phosphodiesterase
T735 1771-1781 NN denotes inhibition
T736 1782-1788 VB denotes occurs
T737 1789-1798 RB denotes partially
T738 1799-1806 IN denotes through
T739 1807-1808 DT denotes a
T740 1809-1816 NN denotes Protein
T741 1817-1823 NN denotes kinase
T742 1824-1837 JJ denotes A-independent
T743 1838-1845 NN denotes pathway
T744 1846-1849 CC denotes and
T745 1850-1853 MD denotes may
T746 1854-1859 VB denotes serve
T747 1860-1862 IN denotes as
T748 1863-1864 DT denotes a
T749 1865-1871 JJ denotes useful
T750 1872-1876 NN denotes tool
T751 1877-1879 IN denotes in
T752 1880-1883 DT denotes the
T753 1884-1895 NN denotes attenuation
T754 1896-1898 IN denotes of
T755 1899-1910 JJ denotes LPS-induced
T756 1911-1923 NN denotes inflammation
T1612 1940-1943 DT denotes The
T1613 1944-1953 JJ denotes bacterial
T1614 1954-1962 NN denotes membrane
T1615 1963-1972 NN denotes component
T1616 1973-1991 NN denotes lipopolysaccharide
T1617 1992-1993 -LRB- denotes (
T1618 1993-1996 NN denotes LPS
T1619 1996-1997 -RRB- denotes )
T1620 1998-2000 VB denotes is
T1621 2001-2008 JJ denotes capable
T1622 2009-2011 IN denotes of
T1623 2012-2022 VB denotes initiating
T1624 2023-2038 NN denotes phosphorylation
T1625 2039-2042 CC denotes and
T1626 2043-2053 NN denotes activation
T1627 2054-2056 IN denotes of
T1628 2057-2065 JJ denotes multiple
T1629 2066-2070 NN denotes host
T1630 2071-2084 JJ denotes intracellular
T1631 2085-2092 NN denotes protein
T1632 2093-2100 NN denotes kinases
T1633 2101-2104 CC denotes and
T1634 2105-2118 NN denotes transcription
T1635 2119-2126 NN denotes factors
T1636 2128-2141 NN denotes Transcription
T1637 2142-2148 NN denotes factor
T1638 2149-2159 NN denotes activation
T1639 2159-2160 -COMMA- denotes ,
T1640 2161-2166 WDT denotes which
T1641 2167-2174 VB denotes results
T1642 2175-2177 IN denotes in
T1643 2178-2181 DT denotes the
T1644 2182-2192 NN denotes modulation
T1645 2193-2195 IN denotes of
T1646 2196-2200 NN denotes gene
T1647 2201-2214 NN denotes transcription
T1648 2215-2218 CC denotes and
T1649 2219-2226 NN denotes protein
T1650 2227-2236 NN denotes synthesis
T1651 2236-2237 -COMMA- denotes ,
T1652 2238-2240 VB denotes is
T1653 2241-2242 DT denotes a
T1654 2243-2251 JJ denotes critical
T1655 2252-2259 NN denotes element
T1656 2260-2262 IN denotes in
T1657 2263-2266 DT denotes the
T1658 2267-2274 NN denotes defense
T1659 2275-2284 NN denotes mechanism
T1660 2285-2287 IN denotes of
T1661 2288-2291 DT denotes the
T1662 2292-2296 NN denotes host
T1663 2297-2303 JJ denotes immune
T1664 2304-2314 NN denotes system.1,2
T1665 2315-2326 JJ denotes LPS-induced
T1666 2327-2340 NN denotes transcription
T1667 2341-2347 NN denotes factor
T1668 2348-2358 NN denotes activation
T1669 2359-2362 VB denotes has
T1670 2363-2367 VB denotes been
T1671 2368-2373 VB denotes shown
T1672 2374-2376 TO denotes to
T1673 2377-2379 VB denotes be
T1674 2380-2381 DT denotes a
T1675 2382-2385 JJ denotes key
T1676 2386-2395 NN denotes regulator
T1677 2396-2398 IN denotes of
T1678 2399-2404 NN denotes tumor
T1679 2405-2413 NN denotes necrosis
T1680 2414-2422 NN denotes factor-α
T1681 2423-2424 -LRB- denotes (
T1682 2424-2429 NN denotes TNF-α
T1683 2429-2430 -RRB- denotes )
T1684 2431-2443 NN denotes production.3
T1685 2444-2449 NN denotes TNF-α
T1686 2450-2452 VB denotes is
T1687 2453-2454 DT denotes a
T1688 2455-2461 JJ denotes potent
T1689 2462-2478 JJ denotes pro-inflammatory
T1690 2479-2487 NN denotes cytokine
T1691 2488-2496 VB denotes involved
T1692 2497-2499 IN denotes in
T1693 2500-2501 DT denotes a
T1694 2502-2506 JJ denotes wide
T1695 2507-2515 NN denotes spectrum
T1696 2516-2518 IN denotes of
T1697 2519-2527 JJ denotes cellular
T1698 2528-2537 NN denotes responses
T1699 2539-2550 RB denotes Furthermore
T1700 2550-2551 -COMMA- denotes ,
T1701 2552-2557 NN denotes TNF-α
T1702 2558-2567 NN denotes synthesis
T1703 2568-2571 MD denotes can
T1704 2572-2574 VB denotes be
T1705 2575-2585 VB denotes attenuated
T1706 2586-2588 IN denotes in
T1707 2589-2595 JJ denotes immune
T1708 2596-2601 NN denotes cells
T1709 2602-2609 VB denotes exposed
T1710 2610-2612 TO denotes to
T1711 2613-2630 NN denotes phosphodiesterase
T1712 2631-2632 -LRB- denotes (
T1713 2632-2635 NN denotes PDE
T1714 2635-2636 -RRB- denotes )
T1715 2637-2647 NN denotes inhibition
T1716 2648-2653 IN denotes after
T1717 2654-2663 NN denotes challenge
T1718 2664-2666 IN denotes by
T1719 2667-2668 DT denotes a
T1720 2669-2676 NN denotes variety
T1721 2677-2679 IN denotes of
T1722 2680-2696 JJ denotes pro-inflammatory
T1723 2697-2709 NN denotes stimulants.4
T1724 2710-2713 DT denotes The
T1725 2714-2723 NN denotes signaling
T1726 2724-2734 NN denotes mechanisms
T1727 2735-2743 VB denotes affected
T1728 2744-2746 IN denotes by
T1729 2747-2750 NN denotes PDE
T1730 2751-2761 NN denotes inhibition
T1731 2761-2762 -COMMA- denotes ,
T1732 2763-2768 WDT denotes which
T1733 2769-2779 RB denotes ultimately
T1734 2780-2784 VB denotes lead
T1735 2785-2787 TO denotes to
T1736 2788-2791 DT denotes the
T1737 2792-2806 NN denotes downregulation
T1738 2807-2809 IN denotes of
T1739 2810-2815 NN denotes TNF-α
T1740 2816-2826 NN denotes production
T1741 2826-2827 -COMMA- denotes ,
T1742 2828-2832 VB denotes have
T1743 2833-2836 RB denotes not
T1744 2837-2841 VB denotes been
T1745 2842-2846 RB denotes well
T1746 2847-2860 VB denotes characterized
T1747 2861-2863 IN denotes in
T1748 2864-2876 JJ denotes inflammatory
T1749 2877-2882 NN denotes cells
T1750 2884-2895 RB denotes Classically
T1751 2895-2896 -COMMA- denotes ,
T1752 2897-2899 PRP denotes it
T1753 2900-2903 VB denotes has
T1754 2904-2908 VB denotes been
T1755 2909-2921 VB denotes demonstrated
T1756 2922-2926 IN denotes that
T1757 2927-2930 NN denotes PDE
T1758 2931-2941 NN denotes inhibition
T1759 2942-2949 VB denotes results
T1760 2950-2952 IN denotes in
T1761 2953-2956 DT denotes the
T1762 2957-2970 JJ denotes intracellular
T1763 2971-2983 NN denotes accumulation
T1764 2984-2986 IN denotes of
T1765 2987-2990 DT denotes the
T1766 2991-2997 JJ denotes second
T1767 2998-3007 NN denotes messenger
T1768 3008-3014 JJ denotes cyclic
T1769 3015-3042 NN denotes adenosine-3,5-monophosphate
T1770 3043-3044 -LRB- denotes (
T1771 3044-3048 NN denotes cAMP
T1772 3048-3049 -RRB- denotes )
T1773 3050-3053 CC denotes and
T1774 3054-3064 JJ denotes subsequent
T1775 3065-3075 NN denotes activation
T1776 3076-3078 IN denotes of
T1777 3079-3086 NN denotes Protein
T1778 3087-3093 NN denotes kinase
T1779 3094-3095 NN denotes A
T1780 3096-3097 -LRB- denotes (
T1781 3097-3100 NN denotes PKA
T1782 3100-3101 -RRB- denotes )
T1783 3101-3103 CD denotes .5
T1784 3104-3107 NN denotes PKA
T1785 3108-3118 NN denotes activation
T1786 3119-3123 RB denotes then
T1787 3124-3129 VB denotes leads
T1788 3130-3132 TO denotes to
T1789 3133-3136 DT denotes the
T1790 3137-3152 NN denotes phosphorylation
T1791 3153-3155 IN denotes of
T1792 3156-3159 DT denotes the
T1793 3160-3173 NN denotes transcription
T1794 3174-3180 NN denotes factor
T1795 3181-3194 JJ denotes cAMP-response
T1796 3195-3202 NN denotes element
T1797 3203-3210 NN denotes binding
T1798 3211-3218 NN denotes protein
T1799 3219-3220 -LRB- denotes (
T1800 3220-3224 NN denotes CREB
T1801 3224-3225 -RRB- denotes )
T1802 3225-3226 -COMMA- denotes ,
T1803 3227-3239 NN denotes transmission
T1804 3240-3242 IN denotes of
T1805 3243-3250 NN denotes signals
T1806 3251-3255 IN denotes into
T1807 3256-3259 DT denotes the
T1808 3260-3267 NN denotes nucleus
T1809 3267-3268 -COMMA- denotes ,
T1810 3269-3272 CC denotes and
T1811 3273-3276 DT denotes the
T1812 3277-3287 JJ denotes subsequent
T1813 3288-3298 NN denotes modulation
T1814 3299-3301 IN denotes of
T1815 3302-3306 NN denotes gene
T1816 3307-3322 NN denotes transcription.6
T1817 3323-3327 DT denotes This
T1818 3328-3338 RB denotes apparently
T1819 3339-3345 JJ denotes simple
T1820 3346-3352 JJ denotes linear
T1821 3353-3360 NN denotes cascade
T1822 3361-3365 VB denotes does
T1823 3366-3369 RB denotes not
T1824 3370-3375 RB denotes fully
T1825 3376-3383 VB denotes explain
T1826 3384-3387 DT denotes the
T1827 3388-3397 NN denotes mechanism
T1828 3398-3400 IN denotes by
T1829 3401-3406 WDT denotes which
T1830 3407-3409 DT denotes an
T1831 3410-3419 NN denotes elevation
T1832 3420-3422 IN denotes in
T1833 3423-3426 DT denotes the
T1834 3427-3440 JJ denotes intracellular
T1835 3441-3445 NN denotes cAMP
T1836 3446-3451 NN denotes level
T1837 3452-3458 VB denotes exerts
T1838 3459-3471 JJ denotes wide-ranging
T1839 3472-3479 NN denotes effects
T1840 3480-3482 IN denotes on
T1841 3483-3491 JJ denotes multiple
T1842 3492-3500 JJ denotes cellular
T1843 3501-3510 NN denotes functions
T1844 3512-3517 EX denotes There
T1845 3518-3520 VB denotes is
T1846 3521-3522 DT denotes a
T1847 3523-3530 VB denotes growing
T1848 3531-3535 NN denotes body
T1849 3536-3538 IN denotes of
T1850 3539-3547 NN denotes evidence
T1851 3548-3558 VB denotes suggesting
T1852 3559-3563 IN denotes that
T1853 3564-3568 NN denotes cAMP
T1854 3569-3572 MD denotes may
T1855 3573-3581 VB denotes function
T1856 3582-3589 IN denotes through
T1857 3590-3594 CC denotes both
T1858 3595-3608 JJ denotes PKA-dependent
T1859 3609-3612 CC denotes and
T1860 3613-3625 JJ denotes -independent
T1861 3626-3640 NN denotes mechanisms.6–8
T1862 3641-3652 JJ denotes LPS-induced
T1863 3653-3663 NN denotes activation
T1864 3664-3666 IN denotes of
T1865 3667-3670 DT denotes the
T1866 3671-3684 NN denotes transcription
T1867 3685-3691 NN denotes factor
T1868 3692-3699 JJ denotes nuclear
T1869 3700-3709 NN denotes factor-κB
T1870 3710-3711 -LRB- denotes (
T1871 3711-3716 NN denotes NF-κB
T1872 3716-3717 -RRB- denotes )
T1873 3718-3721 VB denotes has
T1874 3722-3726 RB denotes also
T1875 3727-3731 VB denotes been
T1876 3732-3735 DT denotes the
T1877 3736-3741 NN denotes focus
T1878 3742-3744 IN denotes of
T1879 3745-3746 DT denotes a
T1880 3747-3752 JJ denotes great
T1881 3753-3757 NN denotes deal
T1882 3758-3760 IN denotes of
T1883 3761-3769 NN denotes research
T1884 3771-3773 PRP denotes It
T1885 3774-3777 VB denotes has
T1886 3778-3782 VB denotes been
T1887 3783-3790 RB denotes clearly
T1888 3791-3803 VB denotes demonstrated
T1889 3804-3808 IN denotes that
T1890 3809-3815 NN denotes agents
T1891 3816-3820 WDT denotes that
T1892 3821-3829 VB denotes increase
T1893 3830-3843 JJ denotes intracellular
T1894 3844-3848 NN denotes cAMP
T1895 3849-3853 RB denotes also
T1896 3854-3861 VB denotes inhibit
T1897 3862-3877 JJ denotes NF-κB-dependent
T1898 3878-3894 JJ denotes pro-inflammatory
T1899 3895-3899 NN denotes gene
T1900 3900-3913 NN denotes transcription
T1901 3913-3914 -COMMA- denotes ,
T1902 3915-3927 RB denotes particularly
T1903 3928-3930 IN denotes of
T1904 3931-3934 DT denotes the
T1905 3935-3940 NN denotes TNF-α
T1906 3941-3947 NN denotes gene.9
T1907 3948-3959 NNP denotes Controversy
T1908 3960-3966 VB denotes exists
T1909 3967-3976 VB denotes regarding
T1910 3977-3980 DT denotes the
T1911 3981-3986 JJ denotes exact
T1912 3987-3996 NN denotes mechanism
T1913 3996-3997 -LRB- denotes (
T1914 3997-3998 NN denotes s
T1915 3998-3999 -RRB- denotes )
T1916 4000-4002 IN denotes by
T1917 4003-4008 WDT denotes which
T1918 4009-4012 NN denotes PDE
T1919 4013-4023 NN denotes inhibition
T1920 4024-4038 VB denotes down-regulates
T1921 4039-4044 NN denotes TNF-α
T1922 4045-4055 NN denotes production
T1923 4057-4070 NN denotes Possibilities
T1924 4071-4078 VB denotes include
T1925 4078-4079 -COMMA- denotes ,
T1926 4080-4083 CC denotes but
T1927 4084-4087 VB denotes are
T1928 4088-4091 RB denotes not
T1929 4092-4099 VB denotes limited
T1930 4100-4102 TO denotes to
T1931 4102-4103 -COMMA- denotes ,
T1932 4104-4114 NN denotes inhibition
T1933 4115-4117 IN denotes of
T1934 4118-4123 NN denotes NF-κB
T1935 4124-4127 NN denotes DNA
T1936 4128-4135 NN denotes binding
T1937 4136-4144 NN denotes activity
T1938 4144-4145 -COMMA- denotes ,
T1939 4146-4160 NN denotes downregulation
T1940 4161-4163 IN denotes of
T1941 4164-4169 NN denotes NF-κB
T1942 4170-4185 JJ denotes transcriptional
T1943 4186-4194 NN denotes activity
T1944 4194-4195 -COMMA- denotes ,
T1945 4196-4205 VB denotes increased
T1946 4206-4210 NN denotes CREB
T1947 4211-4221 NN denotes activation
T1948 4221-4222 -COMMA- denotes ,
T1949 4223-4226 CC denotes and
T1950 4227-4238 NN denotes competition
T1951 4239-4246 IN denotes between
T1952 4247-4252 NN denotes NF-κB
T1953 4253-4256 CC denotes and
T1954 4257-4261 NN denotes CREB
T1955 4262-4265 IN denotes for
T1956 4266-4272 JJ denotes common
T1957 4273-4286 NN denotes co-activators
T1958 4287-4291 JJ denotes such
T1959 4292-4294 IN denotes as
T1960 4295-4299 NN denotes CREB
T1961 4300-4307 NN denotes binding
T1962 4308-4315 NN denotes protein
T1963 4316-4317 -LRB- denotes (
T1964 4317-4320 NN denotes CBP
T1965 4320-4321 -RRB- denotes )
T1966 4323-4325 PRP denotes It
T1967 4326-4328 VB denotes is
T1968 4329-4333 RB denotes also
T1969 4334-4337 RB denotes not
T1970 4338-4343 VB denotes known
T1971 4344-4351 IN denotes whether
T1972 4352-4357 DT denotes these
T1973 4358-4367 NN denotes processes
T1974 4368-4372 VB denotes rely
T1975 4373-4379 RB denotes solely
T1976 4380-4384 IN denotes upon
T1977 4385-4388 DT denotes the
T1978 4389-4399 NN denotes activation
T1979 4400-4402 IN denotes of
T1980 4403-4406 NN denotes PKA
T1981 4408-4417 RB denotes Therefore
T1982 4417-4418 -COMMA- denotes ,
T1983 4419-4422 DT denotes the
T1984 4423-4432 NN denotes objective
T1985 4433-4435 IN denotes of
T1986 4436-4439 DT denotes the
T1987 4440-4447 JJ denotes present
T1988 4448-4453 NN denotes study
T1989 4454-4456 VB denotes is
T1990 4457-4459 TO denotes to
T1991 4460-4469 VB denotes determine
T1992 4470-4473 DT denotes the
T1993 4474-4481 NN denotes effects
T1994 4482-4484 IN denotes of
T1995 4485-4496 JJ denotes nonspecific
T1996 4497-4500 NN denotes PDE
T1997 4501-4511 NN denotes inhibition
T1998 4512-4516 IN denotes with
T1999 4517-4519 NN denotes 1-
T2000 4519-4520 -LRB- denotes [
T2001 4520-4530 NN denotes 5-oxohexyl
T2002 4530-4531 -RRB- denotes ]
T2003 4531-4552 NN denotes -3,7-dimethylxanthine
T2004 4553-4554 -LRB- denotes (
T2005 4554-4568 NN denotes Pentoxifylline
T2006 4568-4569 -COLON- denotes ;
T2007 4570-4573 NN denotes PTX
T2008 4573-4574 -RRB- denotes )
T2009 4575-4577 IN denotes on
T2010 4578-4583 NN denotes NF-κB
T2011 4584-4587 CC denotes and
T2012 4588-4592 NN denotes CREB
T2013 4593-4603 NN denotes activation
T2014 4604-4606 FW denotes in
T2015 4607-4612 FW denotes vitro
T2016 4613-4615 IN denotes in
T2017 4616-4621 JJ denotes human
T2018 4622-4633 JJ denotes mononuclear
T2019 4634-4639 NN denotes cells
T2020 4641-4645 IN denotes With
T2021 4646-4649 DT denotes the
T2022 4650-4653 NN denotes use
T2023 4654-4656 IN denotes of
T2024 4657-4665 JJ denotes specific
T2025 4666-4676 NN denotes inhibitors
T2026 4676-4677 -COMMA- denotes ,
T2027 4678-4680 PRP denotes we
T2028 4681-4685 RB denotes also
T2029 4686-4698 VB denotes investigated
T2030 4699-4702 DT denotes the
T2031 4703-4707 NN denotes role
T2032 4708-4710 IN denotes of
T2033 4711-4714 NN denotes PKA
T2034 4715-4717 IN denotes in
T2035 4718-4729 JJ denotes LPS-induced
T2036 4730-4735 NN denotes TNF-α
T2037 4736-4746 NN denotes production
T2791 0-4 DT denotes this
T2792 5-10 NN denotes study
T2793 11-14 VB denotes was
T2794 4786-4794 VB denotes approved
T2795 4795-4797 IN denotes by
T2796 4798-4801 DT denotes the
T2797 4802-4807 NNP denotes Human
T2798 4808-4816 NNP denotes Research
T2799 4817-4828 NNP denotes Protections
T2800 4829-4836 NNP denotes Program
T2801 4837-4840 CC denotes and
T2802 4841-4844 DT denotes the
T2803 4845-4858 NNP denotes Institutional
T2804 4859-4865 NNP denotes Review
T2805 4866-4872 NNP denotes Board.
T2806 4873-4880 NNP denotes Written
T2807 4881-4888 NN denotes consent
T2808 4889-4891 TO denotes to
T2809 4892-4903 VB denotes participate
T2810 4904-4906 IN denotes in
T2811 4907-4910 DT denotes the
T2812 4911-4916 NN denotes study
T2813 4917-4920 VB denotes was
T2814 4921-4929 VB denotes obtained
T2815 4930-4934 IN denotes from
T2816 4935-4938 DT denotes all
T2817 4939-4949 NN denotes volunteers
T2818 4950-4955 RB denotes prior
T2819 4956-4958 TO denotes to
T2820 4959-4964 NN denotes blood
T2821 4965-4986 JJ denotes donation. Heparinized
T2822 4987-4998 NN denotes Vacutainers
T2823 4999-5003 VB denotes were
T2824 5004-5013 VB denotes purchased
T2825 5014-5018 IN denotes from
T2826 5019-5025 NNP denotes Becton
T2827 5026-5035 NNP denotes Dickinson
T2828 5036-5037 -LRB- denotes (
T2829 5037-5040 NNP denotes San
T2830 5041-5045 NNP denotes Jose
T2831 5045-5046 -COMMA- denotes ,
T2832 5047-5049 NNP denotes CA
T2833 5049-5050 -RRB- denotes )
R369 T474 T473 arg1Of study,this
R370 T477 T475 arg2Of determine,was
R371 T477 T476 arg1Of determine,to
R372 T479 T477 arg2Of effect,determine
R373 T479 T478 arg1Of effect,the
R374 T479 T480 arg1Of effect,of
R375 T479 T484 arg1Of effect,on
R376 T483 T480 arg2Of inhibition,of
R377 T483 T481 arg1Of inhibition,nonspecific
R378 T483 T482 arg1Of inhibition,phosphodiesterase
R379 T487 T485 arg1Of activation,transcription
R380 T487 T486 arg1Of activation,factor
R381 T487 T488 arg1Of activation,and
R382 T488 T484 arg2Of and,on
R383 T488 T496 arg1Of and,in
R384 T491 T489 arg1Of factor-alpha,tumor
R385 T491 T490 arg1Of factor-alpha,necrosis
R386 T491 T492 arg1Of factor-alpha,(
R387 T493 T492 arg2Of TNF-α,(
R388 T494 T492 arg3Of ),(
R389 T495 T488 arg2Of production,and
R390 T495 T491 arg1Of production,factor-alpha
R391 T499 T498 arg2Of LPS,(
R392 T500 T498 arg3Of ),(
R393 T501 T497 arg1Of -stimulated,lipopolysaccharide
R394 T501 T498 arg1Of -stimulated,(
R395 T504 T496 arg2Of cells,in
R396 T504 T501 arg1Of cells,-stimulated
R397 T504 T502 arg1Of cells,human
R398 T504 T503 arg1Of cells,mononuclear
R399 T507 T506 arg1Of production,The
R400 T507 T508 arg1Of production,of
R401 T507 T510 arg1Of production,following
R402 T507 T513 arg1Of production,is
R403 T509 T508 arg2Of TNF-α,of
R404 T512 T510 arg2Of stimulation,following
R405 T512 T511 arg1Of stimulation,LPS
R406 T514 T513 arg2Of one,is
R407 T514 T515 arg1Of one,of
R408 T518 T515 arg2Of steps,of
R409 T518 T516 arg1Of steps,the
R410 T518 T517 arg1Of steps,key
R411 T518 T519 arg1Of steps,in
R412 T521 T522 arg1Of sepsis,and
R413 T522 T519 arg2Of and,in
R414 T522 T520 arg1Of and,bacterial
R415 T523 T522 arg2Of inflammation,and
R416 T525 T524 arg1Of mechanism,The
R417 T525 T526 arg2Of mechanism,by
R418 T525 T527 arg1Of mechanism,which
R419 T525 T538 arg1Of mechanism,remains
R420 T525 T539 arg1Of mechanism,unclear
R421 T529 T528 arg1Of inhibition,phosphodiesterase
R422 T529 T530 arg1Of inhibition,alters
R423 T530 T526 arg1Of alters,by
R424 T530 T533 arg1Of alters,in
R425 T532 T530 arg2Of production,alters
R426 T532 T531 arg1Of production,TNF-α
R427 T535 T533 arg2Of presence,in
R428 T535 T534 arg1Of presence,the
R429 T535 T536 arg1Of presence,of
R430 T537 T536 arg2Of LPS,of
R431 T539 T538 arg2Of unclear,remains
R432 T543 T541 arg1Of cells,Human
R433 T543 T542 arg1Of cells,mononuclear
R434 T543 T544 arg1Of cells,were
R435 T543 T545 arg2Of cells,stimulated
R436 T545 T544 arg2Of stimulated,were
R437 T545 T546 arg1Of stimulated,with
R438 T547 T546 arg2Of LPS,with
R439 T547 T548 arg1Of LPS,(
R440 T547 T552 arg1Of LPS,","
R441 T547 T553 arg1Of LPS,in
R442 T547 T566 arg1Of LPS,","
R443 T550 T548 arg2Of μg/mL,(
R444 T550 T549 arg1Of μg/mL,1
R445 T551 T548 arg3Of ),(
R446 T555 T556 arg1Of presence,and
R447 T556 T553 arg2Of and,in
R448 T556 T554 arg1Of and,the
R449 T556 T558 arg1Of and,of
R450 T557 T556 arg2Of absence,and
R451 T559 T558 arg2Of Pentoxifylline,of
R452 T559 T560 arg1Of Pentoxifylline,(
R453 T561 T562 arg1Of PTX,;
R454 T562 T560 arg2Of ;,(
R455 T564 T562 arg2Of mM,;
R456 T564 T563 arg1Of mM,20
R457 T565 T560 arg3Of ),(
R458 T570 T566 arg2Of inhibitor,","
R459 T570 T567 arg1Of inhibitor,a
R460 T570 T568 arg1Of inhibitor,nonspecific
R461 T570 T569 arg1Of inhibitor,phosphodiesterase
R462 T572 T571 arg1Of blotting,Western
R463 T572 T573 arg1Of blotting,of
R464 T572 T594 arg1Of blotting,was
R465 T572 T595 arg2Of blotting,performed
R466 T576 T574 arg2Of I-κBα,phosphorylated
R467 T576 T575 arg1Of I-κBα,cytoplasmic
R468 T576 T577 arg1Of I-κBα,","
R469 T577 T585 arg1Of ",",and
R470 T580 T577 arg2Of p65,","
R471 T580 T578 arg1Of p65,nuclear
R472 T580 T579 arg1Of p65,factor-κB
R473 T580 T581 arg1Of p65,(
R474 T582 T581 arg2Of NF-κB,(
R475 T583 T581 arg3Of ),(
R476 T585 T573 arg2Of and,of
R477 T585 T584 arg1Of and,","
R478 T590 T585 arg2Of protein,and
R479 T590 T586 arg1Of protein,nuclear
R480 T590 T587 arg1Of protein,cAMP-response
R481 T590 T588 arg1Of protein,element
R482 T590 T589 arg1Of protein,binding
R483 T590 T591 arg1Of protein,(
R484 T592 T591 arg2Of CREB,(
R485 T593 T591 arg3Of ),(
R486 T595 T594 arg2Of performed,was
R487 T597 T596 arg1Of binding,DNA
R488 T597 T598 arg1Of binding,of
R489 T597 T602 arg1Of binding,was
R490 T597 T603 arg2Of binding,verified
R491 T599 T600 arg1Of NF-κB,and
R492 T600 T598 arg2Of and,of
R493 T601 T600 arg2Of CREB,and
R494 T603 T602 arg2Of verified,was
R495 T608 T603 arg1Of assay,verified
R496 T608 T604 arg2Of assay,by
R497 T608 T605 arg1Of assay,electrophoretic
R498 T608 T606 arg1Of assay,mobility
R499 T608 T607 arg1Of assay,shift
R500 T610 T609 arg1Of levels,TNF-α
R501 T610 T611 arg1Of levels,were
R502 T610 T612 arg2Of levels,determined
R503 T612 T611 arg2Of determined,were
R504 T612 T613 arg1Of determined,in
R505 T612 T619 arg1Of determined,in
R506 T615 T613 arg2Of supernatant,in
R507 T615 T614 arg1Of supernatant,the
R508 T615 T616 arg1Of supernatant,of
R509 T618 T616 arg2Of cells,of
R510 T618 T617 arg2Of cells,stimulated
R511 T621 T622 arg1Of presence,and
R512 T623 T622 arg2Of absence,and
R513 T627 T619 arg2Of inhibition,in
R514 T627 T620 arg1Of inhibition,the
R515 T627 T621 arg1Of inhibition,presence
R516 T627 T623 arg1Of inhibition,absence
R517 T627 T624 arg1Of inhibition,Protein
R518 T627 T625 arg1Of inhibition,kinase
R519 T627 T626 arg1Of inhibition,A
R520 T627 T628 arg1Of inhibition,by
R521 T632 T628 arg2Of assay,by
R522 T632 T629 arg1Of assay,an
R523 T632 T630 arg1Of assay,enzyme-linked
R524 T632 T631 arg1Of assay,immunosorbent
R525 T632 T633 arg1Of assay,(
R526 T634 T633 arg2Of ELISA,(
R527 T635 T633 arg3Of ),(
R528 T637 T638 arg1Of PTX,was
R529 T637 T639 arg2Of PTX,demonstrated
R530 T637 T642 arg1Of PTX,reduce
R531 T639 T638 arg2Of demonstrated,was
R532 T642 T639 arg3Of reduce,demonstrated
R533 T642 T640 arg1Of reduce,to
R534 T642 T641 arg1Of reduce,significantly
R535 T645 T643 arg1Of phosphorylation,cytoplasmic
R536 T645 T644 arg1Of phosphorylation,I-κBα
R537 T645 T646 arg1Of phosphorylation,","
R538 T646 T651 arg1Of ",",and
R539 T649 T646 arg2Of phosphorylation,","
R540 T649 T647 arg1Of phosphorylation,nuclear
R541 T649 T648 arg1Of phosphorylation,p65
R542 T651 T642 arg2Of and,reduce
R543 T651 T650 arg1Of and,","
R544 T655 T651 arg2Of activity,and
R545 T655 T652 arg1Of activity,the
R546 T655 T653 arg1Of activity,DNA
R547 T655 T654 arg1Of activity,binding
R548 T655 T656 arg1Of activity,of
R549 T657 T656 arg2Of NF-κB,of
R550 T659 T658 arg2Of contrast,In
R551 T661 T663 arg1Of PTX,enhanced
R552 T663 T658 arg1Of enhanced,In
R553 T663 T660 arg1Of enhanced,","
R554 T663 T662 arg1Of enhanced,markedly
R555 T665 T666 arg1Of phosphorylation,and
R556 T666 T663 arg2Of and,enhanced
R557 T666 T664 arg1Of and,the
R558 T666 T670 arg1Of and,of
R559 T669 T666 arg2Of activity,and
R560 T669 T667 arg1Of activity,DNA
R561 T669 T668 arg1Of activity,binding
R562 T671 T670 arg2Of CREB,of
R563 T672 T674 arg2Of Cells,treated
R564 T672 T679 arg1Of Cells,secreted
R565 T674 T673 arg1Of treated,concomitantly
R566 T674 T675 arg1Of treated,with
R567 T676 T677 arg1Of PTX,and
R568 T677 T675 arg2Of and,with
R569 T678 T677 arg2Of LPS,and
R570 T681 T679 arg2Of levels,secreted
R571 T681 T680 arg1Of levels,similar
R572 T681 T682 arg1Of levels,of
R573 T681 T684 arg1Of levels,in
R574 T683 T682 arg2Of TNF-α,of
R575 T686 T687 arg1Of presence,and
R576 T688 T687 arg2Of absence,and
R577 T692 T684 arg2Of inhibition,in
R578 T692 T685 arg1Of inhibition,the
R579 T692 T686 arg1Of inhibition,presence
R580 T692 T688 arg1Of inhibition,absence
R581 T692 T689 arg1Of inhibition,Protein
R582 T692 T690 arg1Of inhibition,kinase
R583 T692 T691 arg1Of inhibition,A
R584 T696 T694 arg1Of level,The
R585 T696 T695 arg2Of level,increased
R586 T696 T697 arg1Of level,of
R587 T696 T699 arg1Of level,that
R588 T696 T700 arg1Of level,results
R589 T696 T704 arg1Of level,affects
R590 T698 T697 arg2Of cAMP,of
R591 T700 T701 arg1Of results,from
R592 T703 T701 arg2Of inhibition,from
R593 T703 T702 arg1Of inhibition,phosphodiesterase
R594 T704 T709 arg1Of affects,","
R595 T704 T710 modOf affects,resulting
R596 T705 T706 arg1Of cytoplasmic,and
R597 T707 T706 arg2Of nuclear,and
R598 T708 T704 arg2Of events,affects
R599 T708 T705 arg1Of events,cytoplasmic
R600 T708 T707 arg1Of events,nuclear
R601 T710 T711 arg1Of resulting,in
R602 T710 T724 arg1Of resulting,through
R603 T713 T712 arg1Of attenuation,the
R604 T713 T714 arg1Of attenuation,of
R605 T713 T716 arg1Of attenuation,and
R606 T715 T714 arg2Of NF-κB,of
R607 T716 T711 arg2Of and,in
R608 T718 T716 arg2Of activation,and
R609 T718 T717 arg1Of activation,the
R610 T718 T719 arg1Of activation,of
R611 T723 T719 arg2Of binding,of
R612 T723 T720 arg1Of binding,CREB
R613 T723 T721 arg1Of binding,transcriptional
R614 T723 T722 arg1Of binding,DNA
R615 T725 T724 arg2Of pathways,through
R616 T725 T726 arg1Of pathways,that
R617 T725 T727 arg1Of pathways,are
R618 T725 T731 arg1Of pathways,A-independent
R619 T727 T728 arg1Of are,partially
R620 T731 T727 arg2Of A-independent,are
R621 T731 T729 arg1Of A-independent,Protein
R622 T731 T730 arg1Of A-independent,kinase
R623 T735 T733 arg1Of inhibition,PTX-mediated
R624 T735 T734 arg1Of inhibition,phosphodiesterase
R625 T735 T736 arg1Of inhibition,occurs
R626 T735 T745 arg1Of inhibition,may
R627 T735 T746 arg1Of inhibition,serve
R628 T736 T737 arg1Of occurs,partially
R629 T736 T738 arg1Of occurs,through
R630 T736 T744 arg1Of occurs,and
R631 T743 T738 arg2Of pathway,through
R632 T743 T739 arg1Of pathway,a
R633 T743 T740 arg1Of pathway,Protein
R634 T743 T741 arg1Of pathway,kinase
R635 T743 T742 arg1Of pathway,A-independent
R636 T746 T744 arg2Of serve,and
R637 T746 T745 arg2Of serve,may
R638 T746 T747 arg1Of serve,as
R639 T750 T747 arg2Of tool,as
R640 T750 T748 arg1Of tool,a
R641 T750 T749 arg1Of tool,useful
R642 T750 T751 arg1Of tool,in
R643 T753 T751 arg2Of attenuation,in
R644 T753 T752 arg1Of attenuation,the
R645 T753 T754 arg1Of attenuation,of
R646 T756 T754 arg2Of inflammation,of
R647 T756 T755 arg1Of inflammation,LPS-induced
R1298 T1616 T1612 arg1Of lipopolysaccharide,The
R1299 T1616 T1613 arg1Of lipopolysaccharide,bacterial
R1300 T1616 T1614 arg1Of lipopolysaccharide,membrane
R1301 T1616 T1615 arg1Of lipopolysaccharide,component
R1302 T1616 T1617 arg1Of lipopolysaccharide,(
R1303 T1616 T1620 arg1Of lipopolysaccharide,is
R1304 T1616 T1621 arg1Of lipopolysaccharide,capable
R1305 T1616 T1623 arg1Of lipopolysaccharide,initiating
R1306 T1618 T1617 arg2Of LPS,(
R1307 T1619 T1617 arg3Of ),(
R1308 T1621 T1620 arg2Of capable,is
R1309 T1621 T1622 arg1Of capable,of
R1310 T1623 T1622 arg2Of initiating,of
R1311 T1624 T1625 arg1Of phosphorylation,and
R1312 T1625 T1623 arg2Of and,initiating
R1313 T1625 T1627 arg1Of and,of
R1314 T1626 T1625 arg2Of activation,and
R1315 T1632 T1628 arg1Of kinases,multiple
R1316 T1632 T1629 arg1Of kinases,host
R1317 T1632 T1630 arg1Of kinases,intracellular
R1318 T1632 T1631 arg1Of kinases,protein
R1319 T1632 T1633 arg1Of kinases,and
R1320 T1633 T1627 arg2Of and,of
R1321 T1635 T1633 arg2Of factors,and
R1322 T1635 T1634 arg1Of factors,transcription
R1323 T1638 T1636 arg1Of activation,Transcription
R1324 T1638 T1637 arg1Of activation,factor
R1325 T1638 T1639 arg1Of activation,","
R1326 T1638 T1640 arg1Of activation,which
R1327 T1638 T1641 arg1Of activation,results
R1328 T1638 T1652 arg1Of activation,is
R1329 T1641 T1642 arg1Of results,in
R1330 T1644 T1642 arg2Of modulation,in
R1331 T1644 T1643 arg1Of modulation,the
R1332 T1644 T1645 arg1Of modulation,of
R1333 T1647 T1646 arg1Of transcription,gene
R1334 T1647 T1648 arg1Of transcription,and
R1335 T1648 T1645 arg2Of and,of
R1336 T1650 T1648 arg2Of synthesis,and
R1337 T1650 T1649 arg1Of synthesis,protein
R1338 T1652 T1651 arg1Of is,","
R1339 T1655 T1652 arg2Of element,is
R1340 T1655 T1653 arg1Of element,a
R1341 T1655 T1654 arg1Of element,critical
R1342 T1655 T1656 arg1Of element,in
R1343 T1659 T1656 arg2Of mechanism,in
R1344 T1659 T1657 arg1Of mechanism,the
R1345 T1659 T1658 arg1Of mechanism,defense
R1346 T1659 T1660 arg1Of mechanism,of
R1347 T1664 T1660 arg2Of "system.1,2",of
R1348 T1664 T1661 arg1Of "system.1,2",the
R1349 T1664 T1662 arg1Of "system.1,2",host
R1350 T1664 T1663 arg1Of "system.1,2",immune
R1351 T1668 T1665 arg1Of activation,LPS-induced
R1352 T1668 T1666 arg1Of activation,transcription
R1353 T1668 T1667 arg1Of activation,factor
R1354 T1668 T1669 arg1Of activation,has
R1355 T1668 T1670 arg1Of activation,been
R1356 T1668 T1671 arg2Of activation,shown
R1357 T1668 T1673 arg1Of activation,be
R1358 T1671 T1669 arg2Of shown,has
R1359 T1671 T1670 arg2Of shown,been
R1360 T1673 T1671 arg3Of be,shown
R1361 T1673 T1672 arg1Of be,to
R1362 T1676 T1673 arg2Of regulator,be
R1363 T1676 T1674 arg1Of regulator,a
R1364 T1676 T1675 arg1Of regulator,key
R1365 T1676 T1677 arg1Of regulator,of
R1366 T1676 T1686 modOf regulator,is
R1367 T1680 T1677 arg2Of factor-α,of
R1368 T1680 T1678 arg1Of factor-α,tumor
R1369 T1680 T1679 arg1Of factor-α,necrosis
R1370 T1682 T1681 arg2Of TNF-α,(
R1371 T1683 T1681 arg3Of ),(
R1372 T1685 T1681 arg1Of TNF-α,(
R1373 T1685 T1684 arg1Of TNF-α,production.3
R1374 T1685 T1686 arg1Of TNF-α,is
R1375 T1690 T1686 arg2Of cytokine,is
R1376 T1690 T1687 arg1Of cytokine,a
R1377 T1690 T1688 arg1Of cytokine,potent
R1378 T1690 T1689 arg1Of cytokine,pro-inflammatory
R1379 T1690 T1691 arg2Of cytokine,involved
R1380 T1691 T1692 arg1Of involved,in
R1381 T1695 T1692 arg2Of spectrum,in
R1382 T1695 T1693 arg1Of spectrum,a
R1383 T1695 T1694 arg1Of spectrum,wide
R1384 T1695 T1696 arg1Of spectrum,of
R1385 T1698 T1696 arg2Of responses,of
R1386 T1698 T1697 arg1Of responses,cellular
R1387 T1702 T1701 arg1Of synthesis,TNF-α
R1388 T1702 T1703 arg1Of synthesis,can
R1389 T1702 T1704 arg1Of synthesis,be
R1390 T1702 T1705 arg2Of synthesis,attenuated
R1391 T1705 T1703 arg2Of attenuated,can
R1392 T1705 T1704 arg2Of attenuated,be
R1393 T1705 T1706 arg1Of attenuated,in
R1394 T1705 T1716 arg1Of attenuated,after
R1395 T1708 T1706 arg2Of cells,in
R1396 T1708 T1707 arg1Of cells,immune
R1397 T1708 T1709 arg2Of cells,exposed
R1398 T1709 T1710 arg1Of exposed,to
R1399 T1711 T1712 arg1Of phosphodiesterase,(
R1400 T1713 T1712 arg2Of PDE,(
R1401 T1714 T1712 arg3Of ),(
R1402 T1715 T1710 arg2Of inhibition,to
R1403 T1715 T1711 arg1Of inhibition,phosphodiesterase
R1404 T1717 T1716 arg2Of challenge,after
R1405 T1717 T1718 arg1Of challenge,by
R1406 T1720 T1718 arg2Of variety,by
R1407 T1720 T1719 arg1Of variety,a
R1408 T1720 T1721 arg1Of variety,of
R1409 T1723 T1721 arg2Of stimulants.4,of
R1410 T1723 T1722 arg1Of stimulants.4,pro-inflammatory
R1411 T1726 T1724 arg1Of mechanisms,The
R1412 T1726 T1725 arg1Of mechanisms,signaling
R1413 T1726 T1727 arg2Of mechanisms,affected
R1414 T1726 T1731 arg1Of mechanisms,","
R1415 T1726 T1732 arg1Of mechanisms,which
R1416 T1726 T1734 arg1Of mechanisms,lead
R1417 T1726 T1742 arg1Of mechanisms,have
R1418 T1726 T1744 arg1Of mechanisms,been
R1419 T1726 T1746 arg2Of mechanisms,characterized
R1420 T1730 T1727 arg1Of inhibition,affected
R1421 T1730 T1728 arg2Of inhibition,by
R1422 T1730 T1729 arg1Of inhibition,PDE
R1423 T1734 T1733 arg1Of lead,ultimately
R1424 T1734 T1735 arg1Of lead,to
R1425 T1737 T1735 arg2Of downregulation,to
R1426 T1737 T1736 arg1Of downregulation,the
R1427 T1737 T1738 arg1Of downregulation,of
R1428 T1740 T1738 arg2Of production,of
R1429 T1740 T1739 arg1Of production,TNF-α
R1430 T1746 T1699 arg1Of characterized,Furthermore
R1431 T1746 T1700 arg1Of characterized,","
R1432 T1746 T1703 modOf characterized,can
R1433 T1746 T1741 arg1Of characterized,","
R1434 T1746 T1742 arg2Of characterized,have
R1435 T1746 T1743 arg1Of characterized,not
R1436 T1746 T1744 arg2Of characterized,been
R1437 T1746 T1745 arg1Of characterized,well
R1438 T1746 T1747 arg1Of characterized,in
R1439 T1749 T1747 arg2Of cells,in
R1440 T1749 T1748 arg1Of cells,inflammatory
R1441 T1752 T1753 arg1Of it,has
R1442 T1752 T1754 arg1Of it,been
R1443 T1752 T1755 arg2Of it,demonstrated
R1444 T1755 T1750 arg1Of demonstrated,Classically
R1445 T1755 T1751 arg1Of demonstrated,","
R1446 T1755 T1753 arg2Of demonstrated,has
R1447 T1755 T1754 arg2Of demonstrated,been
R1448 T1758 T1757 arg1Of inhibition,PDE
R1449 T1758 T1759 arg1Of inhibition,results
R1450 T1759 T1760 arg1Of results,in
R1451 T1759 T1773 arg1Of results,and
R1452 T1763 T1760 arg2Of accumulation,in
R1453 T1763 T1761 arg1Of accumulation,the
R1454 T1763 T1762 arg1Of accumulation,intracellular
R1455 T1763 T1764 arg1Of accumulation,of
R1456 T1769 T1764 arg2Of "adenosine-3,5-monophosphate",of
R1457 T1769 T1765 arg1Of "adenosine-3,5-monophosphate",the
R1458 T1769 T1766 arg1Of "adenosine-3,5-monophosphate",second
R1459 T1769 T1767 arg1Of "adenosine-3,5-monophosphate",messenger
R1460 T1769 T1768 arg1Of "adenosine-3,5-monophosphate",cyclic
R1461 T1769 T1770 arg1Of "adenosine-3,5-monophosphate",(
R1462 T1771 T1770 arg2Of cAMP,(
R1463 T1772 T1770 arg3Of ),(
R1464 T1773 T1810 arg1Of and,and
R1465 T1775 T1774 arg1Of activation,subsequent
R1466 T1775 T1776 arg1Of activation,of
R1467 T1775 T1787 arg1Of activation,leads
R1468 T1781 T1780 arg2Of PKA,(
R1469 T1782 T1780 arg3Of ),(
R1470 T1785 T1776 arg2Of activation,of
R1471 T1785 T1777 arg1Of activation,Protein
R1472 T1785 T1778 arg1Of activation,kinase
R1473 T1785 T1779 arg1Of activation,A
R1474 T1785 T1780 arg1Of activation,(
R1475 T1785 T1783 arg1Of activation,.5
R1476 T1785 T1784 arg1Of activation,PKA
R1477 T1787 T1773 arg2Of leads,and
R1478 T1787 T1786 arg1Of leads,then
R1479 T1787 T1788 arg1Of leads,to
R1480 T1790 T1788 arg2Of phosphorylation,to
R1481 T1790 T1789 arg1Of phosphorylation,the
R1482 T1790 T1791 arg1Of phosphorylation,of
R1483 T1798 T1793 arg1Of protein,transcription
R1484 T1798 T1794 arg1Of protein,factor
R1485 T1798 T1795 arg1Of protein,cAMP-response
R1486 T1798 T1796 arg1Of protein,element
R1487 T1798 T1797 arg1Of protein,binding
R1488 T1798 T1799 arg1Of protein,(
R1489 T1798 T1802 arg1Of protein,","
R1490 T1800 T1799 arg2Of CREB,(
R1491 T1801 T1799 arg3Of ),(
R1492 T1802 T1791 arg2Of ",",of
R1493 T1802 T1792 arg1Of ",",the
R1494 T1803 T1802 arg2Of transmission,","
R1495 T1803 T1804 arg1Of transmission,of
R1496 T1803 T1806 arg1Of transmission,into
R1497 T1805 T1804 arg2Of signals,of
R1498 T1808 T1806 arg2Of nucleus,into
R1499 T1808 T1807 arg1Of nucleus,the
R1500 T1810 T1755 arg3Of and,demonstrated
R1501 T1810 T1756 arg1Of and,that
R1502 T1810 T1809 arg1Of and,","
R1503 T1813 T1811 arg1Of modulation,the
R1504 T1813 T1812 arg1Of modulation,subsequent
R1505 T1813 T1814 arg1Of modulation,of
R1506 T1813 T1822 arg1Of modulation,does
R1507 T1813 T1825 arg1Of modulation,explain
R1508 T1816 T1815 arg1Of transcription.6,gene
R1509 T1819 T1818 arg1Of simple,apparently
R1510 T1821 T1814 arg2Of cascade,of
R1511 T1821 T1816 arg1Of cascade,transcription.6
R1512 T1821 T1817 arg1Of cascade,This
R1513 T1821 T1819 arg1Of cascade,simple
R1514 T1821 T1820 arg1Of cascade,linear
R1515 T1825 T1810 arg2Of explain,and
R1516 T1825 T1822 arg2Of explain,does
R1517 T1825 T1823 arg1Of explain,not
R1518 T1825 T1824 arg1Of explain,fully
R1519 T1827 T1825 arg2Of mechanism,explain
R1520 T1827 T1826 arg1Of mechanism,the
R1521 T1827 T1828 arg2Of mechanism,by
R1522 T1827 T1829 arg1Of mechanism,which
R1523 T1831 T1830 arg1Of elevation,an
R1524 T1831 T1832 arg1Of elevation,in
R1525 T1831 T1837 arg1Of elevation,exerts
R1526 T1836 T1832 arg2Of level,in
R1527 T1836 T1833 arg1Of level,the
R1528 T1836 T1834 arg1Of level,intracellular
R1529 T1836 T1835 arg1Of level,cAMP
R1530 T1837 T1828 arg1Of exerts,by
R1531 T1837 T1840 arg1Of exerts,on
R1532 T1839 T1837 arg2Of effects,exerts
R1533 T1839 T1838 arg1Of effects,wide-ranging
R1534 T1843 T1840 arg2Of functions,on
R1535 T1843 T1841 arg1Of functions,multiple
R1536 T1843 T1842 arg1Of functions,cellular
R1537 T1844 T1845 arg1Of There,is
R1538 T1848 T1845 arg2Of body,is
R1539 T1848 T1846 arg1Of body,a
R1540 T1848 T1847 arg1Of body,growing
R1541 T1848 T1849 arg1Of body,of
R1542 T1848 T1851 arg1Of body,suggesting
R1543 T1850 T1849 arg2Of evidence,of
R1544 T1853 T1854 arg1Of cAMP,may
R1545 T1853 T1855 arg1Of cAMP,function
R1546 T1855 T1851 arg2Of function,suggesting
R1547 T1855 T1852 arg1Of function,that
R1548 T1855 T1854 arg2Of function,may
R1549 T1855 T1856 arg1Of function,through
R1550 T1858 T1859 arg1Of PKA-dependent,and
R1551 T1860 T1859 arg2Of -independent,and
R1552 T1861 T1856 arg2Of mechanisms.6–8,through
R1553 T1861 T1857 arg1Of mechanisms.6–8,both
R1554 T1861 T1858 arg1Of mechanisms.6–8,PKA-dependent
R1555 T1861 T1860 arg1Of mechanisms.6–8,-independent
R1556 T1863 T1862 arg1Of activation,LPS-induced
R1557 T1863 T1864 arg1Of activation,of
R1558 T1863 T1873 arg1Of activation,has
R1559 T1863 T1875 arg1Of activation,been
R1560 T1869 T1864 arg2Of factor-κB,of
R1561 T1869 T1865 arg1Of factor-κB,the
R1562 T1869 T1866 arg1Of factor-κB,transcription
R1563 T1869 T1867 arg1Of factor-κB,factor
R1564 T1869 T1868 arg1Of factor-κB,nuclear
R1565 T1869 T1870 arg1Of factor-κB,(
R1566 T1871 T1870 arg2Of NF-κB,(
R1567 T1872 T1870 arg3Of ),(
R1568 T1875 T1873 arg2Of been,has
R1569 T1875 T1874 arg1Of been,also
R1570 T1877 T1875 arg2Of focus,been
R1571 T1877 T1876 arg1Of focus,the
R1572 T1877 T1878 arg1Of focus,of
R1573 T1881 T1878 arg2Of deal,of
R1574 T1881 T1879 arg1Of deal,a
R1575 T1881 T1880 arg1Of deal,great
R1576 T1881 T1882 arg1Of deal,of
R1577 T1883 T1882 arg2Of research,of
R1578 T1884 T1885 arg1Of It,has
R1579 T1884 T1886 arg1Of It,been
R1580 T1884 T1888 arg2Of It,demonstrated
R1581 T1888 T1885 arg2Of demonstrated,has
R1582 T1888 T1886 arg2Of demonstrated,been
R1583 T1888 T1887 arg1Of demonstrated,clearly
R1584 T1890 T1891 arg1Of agents,that
R1585 T1890 T1892 arg1Of agents,increase
R1586 T1890 T1896 arg1Of agents,inhibit
R1587 T1894 T1892 arg2Of cAMP,increase
R1588 T1894 T1893 arg1Of cAMP,intracellular
R1589 T1896 T1888 arg3Of inhibit,demonstrated
R1590 T1896 T1889 arg1Of inhibit,that
R1591 T1896 T1895 arg1Of inhibit,also
R1592 T1900 T1896 arg2Of transcription,inhibit
R1593 T1900 T1897 arg1Of transcription,NF-κB-dependent
R1594 T1900 T1898 arg1Of transcription,pro-inflammatory
R1595 T1900 T1899 arg1Of transcription,gene
R1596 T1900 T1901 arg1Of transcription,","
R1597 T1900 T1903 arg1Of transcription,of
R1598 T1903 T1902 arg1Of of,particularly
R1599 T1906 T1903 arg2Of gene.9,of
R1600 T1906 T1904 arg1Of gene.9,the
R1601 T1906 T1905 arg1Of gene.9,TNF-α
R1602 T1907 T1908 arg1Of Controversy,exists
R1603 T1908 T1909 arg1Of exists,regarding
R1604 T1912 T1909 arg2Of mechanism,regarding
R1605 T1912 T1910 arg1Of mechanism,the
R1606 T1912 T1911 arg1Of mechanism,exact
R1607 T1912 T1913 arg1Of mechanism,(
R1608 T1912 T1916 arg2Of mechanism,by
R1609 T1912 T1917 arg1Of mechanism,which
R1610 T1914 T1913 arg2Of s,(
R1611 T1915 T1913 arg3Of ),(
R1612 T1919 T1918 arg1Of inhibition,PDE
R1613 T1919 T1920 arg1Of inhibition,down-regulates
R1614 T1920 T1916 arg1Of down-regulates,by
R1615 T1922 T1920 arg2Of production,down-regulates
R1616 T1922 T1921 arg1Of production,TNF-α
R1617 T1923 T1924 arg1Of Possibilities,include
R1618 T1923 T1927 arg1Of Possibilities,are
R1619 T1923 T1929 arg2Of Possibilities,limited
R1620 T1924 T1926 arg1Of include,but
R1621 T1926 T1925 arg1Of but,","
R1622 T1926 T1931 arg1Of but,","
R1623 T1929 T1926 arg2Of limited,but
R1624 T1929 T1927 arg2Of limited,are
R1625 T1929 T1928 arg1Of limited,not
R1626 T1929 T1930 arg1Of limited,to
R1627 T1932 T1933 arg1Of inhibition,of
R1628 T1932 T1945 arg1Of inhibition,increased
R1629 T1937 T1934 arg1Of activity,NF-κB
R1630 T1937 T1935 arg1Of activity,DNA
R1631 T1937 T1936 arg1Of activity,binding
R1632 T1937 T1938 arg1Of activity,","
R1633 T1938 T1933 arg2Of ",",of
R1634 T1939 T1938 arg2Of downregulation,","
R1635 T1939 T1940 arg1Of downregulation,of
R1636 T1943 T1940 arg2Of activity,of
R1637 T1943 T1941 arg1Of activity,NF-κB
R1638 T1943 T1942 arg1Of activity,transcriptional
R1639 T1945 T1931 arg2Of increased,","
R1640 T1945 T1944 arg1Of increased,","
R1641 T1947 T1946 arg1Of activation,CREB
R1642 T1947 T1949 arg1Of activation,and
R1643 T1949 T1945 arg2Of and,increased
R1644 T1949 T1948 arg1Of and,","
R1645 T1950 T1949 arg2Of competition,and
R1646 T1950 T1951 arg1Of competition,between
R1647 T1952 T1953 arg1Of NF-κB,and
R1648 T1953 T1951 arg2Of and,between
R1649 T1953 T1955 arg1Of and,for
R1650 T1954 T1953 arg2Of CREB,and
R1651 T1957 T1955 arg2Of co-activators,for
R1652 T1957 T1956 arg1Of co-activators,common
R1653 T1957 T1959 arg1Of co-activators,as
R1654 T1959 T1958 arg1Of as,such
R1655 T1962 T1959 arg2Of protein,as
R1656 T1962 T1960 arg1Of protein,CREB
R1657 T1962 T1961 arg1Of protein,binding
R1658 T1962 T1963 arg1Of protein,(
R1659 T1964 T1963 arg2Of CBP,(
R1660 T1965 T1963 arg3Of ),(
R1661 T1966 T1967 arg1Of It,is
R1662 T1966 T1970 arg2Of It,known
R1663 T1970 T1967 arg2Of known,is
R1664 T1970 T1968 arg1Of known,also
R1665 T1970 T1969 arg1Of known,not
R1666 T1973 T1972 arg1Of processes,these
R1667 T1973 T1974 arg1Of processes,rely
R1668 T1974 T1970 arg3Of rely,known
R1669 T1974 T1971 arg1Of rely,whether
R1670 T1974 T1975 arg1Of rely,solely
R1671 T1974 T1976 arg1Of rely,upon
R1672 T1978 T1976 arg2Of activation,upon
R1673 T1978 T1977 arg1Of activation,the
R1674 T1978 T1979 arg1Of activation,of
R1675 T1980 T1979 arg2Of PKA,of
R1676 T1984 T1983 arg1Of objective,the
R1677 T1984 T1985 arg1Of objective,of
R1678 T1984 T1989 arg1Of objective,is
R1679 T1988 T1985 arg2Of study,of
R1680 T1988 T1986 arg1Of study,the
R1681 T1988 T1987 arg1Of study,present
R1682 T1989 T1981 arg1Of is,Therefore
R1683 T1989 T1982 arg1Of is,","
R1684 T1991 T1989 arg2Of determine,is
R1685 T1991 T1990 arg1Of determine,to
R1686 T1991 T1998 arg1Of determine,with
R1687 T1991 T2015 arg1Of determine,vitro
R1688 T1991 T2016 arg1Of determine,in
R1689 T1993 T1991 arg2Of effects,determine
R1690 T1993 T1992 arg1Of effects,the
R1691 T1993 T1994 arg1Of effects,of
R1692 T1997 T1994 arg2Of inhibition,of
R1693 T1997 T1995 arg1Of inhibition,nonspecific
R1694 T1997 T1996 arg1Of inhibition,PDE
R1695 T2001 T2000 arg2Of 5-oxohexyl,[
R1696 T2002 T2000 arg3Of ],[
R1697 T2003 T1998 arg2Of "-3,7-dimethylxanthine",with
R1698 T2003 T1999 arg1Of "-3,7-dimethylxanthine",1-
R1699 T2003 T2000 arg1Of "-3,7-dimethylxanthine",[
R1700 T2003 T2004 arg1Of "-3,7-dimethylxanthine",(
R1701 T2003 T2009 arg1Of "-3,7-dimethylxanthine",on
R1702 T2005 T2004 arg2Of Pentoxifylline,(
R1703 T2005 T2006 arg1Of Pentoxifylline,;
R1704 T2007 T2006 arg2Of PTX,;
R1705 T2008 T2004 arg3Of ),(
R1706 T2010 T2011 arg1Of NF-κB,and
R1707 T2012 T2011 arg2Of CREB,and
R1708 T2013 T2009 arg2Of activation,on
R1709 T2013 T2010 arg1Of activation,NF-κB
R1710 T2013 T2012 arg1Of activation,CREB
R1711 T2015 T2014 arg1Of vitro,in
R1712 T2019 T2016 arg2Of cells,in
R1713 T2019 T2017 arg1Of cells,human
R1714 T2019 T2018 arg1Of cells,mononuclear
R1715 T2022 T2020 arg2Of use,With
R1716 T2022 T2021 arg1Of use,the
R1717 T2022 T2023 arg1Of use,of
R1718 T2025 T2023 arg2Of inhibitors,of
R1719 T2025 T2024 arg1Of inhibitors,specific
R1720 T2027 T2029 arg1Of we,investigated
R1721 T2029 T2020 arg1Of investigated,With
R1722 T2029 T2026 arg1Of investigated,","
R1723 T2029 T2028 arg1Of investigated,also
R1724 T2031 T2029 arg2Of role,investigated
R1725 T2031 T2030 arg1Of role,the
R1726 T2031 T2032 arg1Of role,of
R1727 T2031 T2034 arg1Of role,in
R1728 T2033 T2032 arg2Of PKA,of
R1729 T2037 T2034 arg2Of production,in
R1730 T2037 T2035 arg1Of production,LPS-induced
R1731 T2037 T2036 arg1Of production,TNF-α
R2218 T2792 T2791 arg1Of study,this
R2219 T2792 T2793 arg1Of study,was
R2220 T2792 T2794 arg2Of study,approved
R2221 T2794 T2793 arg2Of approved,was
R2222 T2794 T2810 arg1Of approved,in
R2223 T2800 T2796 arg1Of Program,the
R2224 T2800 T2797 arg1Of Program,Human
R2225 T2800 T2798 arg1Of Program,Research
R2226 T2800 T2799 arg1Of Program,Protections
R2227 T2800 T2801 arg1Of Program,and
R2228 T2801 T2794 arg1Of and,approved
R2229 T2801 T2795 arg2Of and,by
R2230 T2806 T2803 arg1Of Written,Institutional
R2231 T2806 T2804 arg1Of Written,Review
R2232 T2806 T2805 arg1Of Written,Board.
R2233 T2807 T2801 arg2Of consent,and
R2234 T2807 T2802 arg1Of consent,the
R2235 T2807 T2806 arg1Of consent,Written
R2236 T2807 T2808 modOf consent,to
R2237 T2809 T2808 arg1Of participate,to
R2238 T2812 T2811 arg1Of study,the
R2239 T2812 T2813 arg1Of study,was
R2240 T2812 T2814 arg2Of study,obtained
R2241 T2814 T2813 arg2Of obtained,was
R2242 T2814 T2815 arg1Of obtained,from
R2243 T2814 T2818 arg1Of obtained,prior
R2244 T2817 T2815 arg2Of volunteers,from
R2245 T2817 T2816 arg1Of volunteers,all
R2246 T2818 T2819 arg1Of prior,to
R2247 T2820 T2819 arg2Of blood,to
R2248 T2822 T2821 arg1Of Vacutainers,"donation. Heparinized"
R2249 T2822 T2823 arg1Of Vacutainers,were
R2250 T2822 T2824 arg2Of Vacutainers,purchased
R2251 T2824 T2810 arg2Of purchased,in
R2252 T2824 T2813 modOf purchased,was
R2253 T2824 T2823 arg2Of purchased,were
R2254 T2824 T2825 arg1Of purchased,from
R2255 T2827 T2825 arg2Of Dickinson,from
R2256 T2827 T2826 arg1Of Dickinson,Becton
R2257 T2827 T2828 arg1Of Dickinson,(
R2258 T2830 T2828 arg2Of Jose,(
R2259 T2830 T2829 arg1Of Jose,San
R2260 T2830 T2831 arg1Of Jose,","
R2261 T2832 T2831 arg2Of CA,","
R2262 T2833 T2828 arg3Of ),(

bionlp-st-ge-2016-spacy-parsed

Id Subject Object Predicate Lexical cue
T162 72-82 NN denotes inhibition
T163 83-85 IN denotes on
T164 86-99 NN denotes transcription
T165 100-106 NN denotes factor
T166 107-117 NN denotes activation
T167 118-121 CC denotes and
T168 122-127 NN denotes tumor
T169 128-136 NN denotes necrosis
T170 137-149 NN denotes factor-alpha
T171 150-151 -LRB- denotes (
T172 151-156 NNP denotes TNF-α
T173 156-157 -RRB- denotes )
T174 158-168 NN denotes production
T175 169-171 IN denotes in
T176 172-190 NN denotes lipopolysaccharide
T177 191-192 -LRB- denotes (
T178 192-195 NNP denotes LPS
T179 195-196 -RRB- denotes )
T180 196-197 : denotes -
T181 197-207 VBN denotes stimulated
T182 208-213 JJ denotes human
T183 214-225 NN denotes mononuclear
T184 226-231 NNS denotes cells
T185 231-232 . denotes .
T186 234-246 NNP denotes INTRODUCTION
T187 247-250 DT denotes The
T188 251-261 NN denotes production
T189 262-264 IN denotes of
T190 265-270 NNP denotes TNF-α
T191 271-280 VBG denotes following
T192 281-284 NNP denotes LPS
T193 285-296 NN denotes stimulation
T194 297-299 VBZ denotes is
T195 300-303 CD denotes one
T196 304-306 IN denotes of
T197 307-310 DT denotes the
T198 311-314 JJ denotes key
T199 315-320 NNS denotes steps
T200 321-323 IN denotes in
T201 324-333 JJ denotes bacterial
T202 334-340 NN denotes sepsis
T203 341-344 CC denotes and
T204 345-357 NN denotes inflammation
T205 357-358 . denotes .
T206 359-362 DT denotes The
T207 363-372 NN denotes mechanism
T208 373-375 IN denotes by
T209 376-381 WDT denotes which
T210 382-399 NN denotes phosphodiesterase
T211 400-410 NN denotes inhibition
T212 411-417 VBZ denotes alters
T213 418-423 JJ denotes TNF-α
T214 424-434 NN denotes production
T215 435-437 IN denotes in
T216 438-441 DT denotes the
T217 442-450 NN denotes presence
T218 451-453 IN denotes of
T219 454-457 NNP denotes LPS
T220 458-465 VBZ denotes remains
T221 466-473 JJ denotes unclear
T222 473-474 . denotes .
T223 476-483 NNP denotes METHODS
T224 484-489 NNP denotes Human
T225 490-501 NN denotes mononuclear
T226 502-507 NNS denotes cells
T227 508-512 VBD denotes were
T228 513-523 VBN denotes stimulated
T229 524-528 IN denotes with
T230 529-532 NNP denotes LPS
T231 533-534 -LRB- denotes (
T232 534-535 CD denotes 1
T233 536-538 NN denotes μg
T234 538-539 NN denotes /
T235 539-541 NNP denotes mL
T236 541-542 -RRB- denotes )
T237 542-543 , denotes ,
T238 544-546 IN denotes in
T239 547-550 DT denotes the
T240 551-559 NN denotes presence
T241 560-563 CC denotes and
T242 564-571 NN denotes absence
T243 572-574 IN denotes of
T244 575-589 NNP denotes Pentoxifylline
T245 590-591 -LRB- denotes (
T246 591-594 NNP denotes PTX
T247 594-595 : denotes ;
T248 596-598 CD denotes 20
T249 599-601 NNP denotes mM
T250 601-602 -RRB- denotes )
T251 602-603 , denotes ,
T252 604-605 DT denotes a
T253 606-617 JJ denotes nonspecific
T254 618-635 NN denotes phosphodiesterase
T255 636-645 NN denotes inhibitor
T256 645-646 . denotes .
T257 647-654 JJ denotes Western
T258 655-663 VBG denotes blotting
T259 664-666 IN denotes of
T260 667-681 VBN denotes phosphorylated
T261 682-693 JJ denotes cytoplasmic
T262 694-699 NNP denotes I-κBα
T263 699-700 , denotes ,
T264 701-708 JJ denotes nuclear
T265 709-718 NNP denotes factor-κB
T266 719-722 NNS denotes p65
T267 723-724 -LRB- denotes (
T268 724-729 NN denotes NF-κB
T269 729-730 -RRB- denotes )
T270 730-731 , denotes ,
T271 732-735 CC denotes and
T272 736-743 JJ denotes nuclear
T273 744-757 JJ denotes cAMP-response
T274 758-765 NN denotes element
T275 766-773 JJ denotes binding
T276 774-781 NN denotes protein
T277 782-783 -LRB- denotes (
T278 783-787 NNP denotes CREB
T279 787-788 -RRB- denotes )
T280 789-792 VBD denotes was
T281 793-802 VBN denotes performed
T282 802-803 . denotes .
T283 804-807 NNP denotes DNA
T284 808-815 JJ denotes binding
T285 816-818 IN denotes of
T286 819-824 NNP denotes NF-κB
T287 825-828 CC denotes and
T288 829-833 NNP denotes CREB
T289 834-837 VBD denotes was
T290 838-846 VBN denotes verified
T291 847-849 IN denotes by
T292 850-865 JJ denotes electrophoretic
T293 866-874 NN denotes mobility
T294 875-880 NN denotes shift
T295 881-886 NN denotes assay
T296 886-887 . denotes .
T297 888-893 JJ denotes TNF-α
T298 894-900 NNS denotes levels
T299 901-905 VBD denotes were
T300 906-916 VBN denotes determined
T301 917-919 IN denotes in
T302 920-923 DT denotes the
T303 924-935 NN denotes supernatant
T304 936-938 IN denotes of
T305 939-949 VBN denotes stimulated
T306 950-955 NNS denotes cells
T307 956-958 IN denotes in
T308 959-962 DT denotes the
T309 963-971 NN denotes presence
T310 972-975 CC denotes and
T311 976-983 NN denotes absence
T312 984-991 NNP denotes Protein
T313 992-998 NN denotes kinase
T314 999-1000 DT denotes A
T315 1001-1011 NN denotes inhibition
T316 1012-1014 IN denotes by
T317 1015-1017 DT denotes an
T318 1018-1031 JJ denotes enzyme-linked
T319 1032-1045 JJ denotes immunosorbent
T320 1046-1051 NN denotes assay
T321 1052-1053 -LRB- denotes (
T322 1053-1058 NNP denotes ELISA
T323 1058-1059 -RRB- denotes )
T324 1059-1060 . denotes .
T325 1062-1069 NNS denotes RESULTS
T326 1070-1073 VBP denotes PTX
T327 1074-1077 VBD denotes was
T328 1078-1090 VBN denotes demonstrated
T329 1091-1093 TO denotes to
T330 1094-1107 RB denotes significantly
T331 1108-1114 VB denotes reduce
T332 1115-1126 JJ denotes cytoplasmic
T333 1127-1132 JJ denotes I-κBα
T334 1133-1148 NN denotes phosphorylation
T335 1148-1149 , denotes ,
T336 1150-1157 JJ denotes nuclear
T337 1158-1161 NNS denotes p65
T338 1162-1177 NN denotes phosphorylation
T339 1177-1178 , denotes ,
T340 1179-1182 CC denotes and
T341 1183-1186 DT denotes the
T342 1187-1190 NNP denotes DNA
T343 1191-1198 JJ denotes binding
T344 1199-1207 NN denotes activity
T345 1208-1210 IN denotes of
T346 1211-1216 NN denotes NF-κB
T347 1216-1217 . denotes .
T348 1218-1220 IN denotes In
T349 1221-1229 NN denotes contrast
T350 1229-1230 , denotes ,
T351 1231-1234 NNP denotes PTX
T352 1235-1243 RB denotes markedly
T353 1244-1252 VBD denotes enhanced
T354 1253-1256 DT denotes the
T355 1257-1272 NN denotes phosphorylation
T356 1273-1276 CC denotes and
T357 1277-1280 NN denotes DNA
T358 1281-1288 JJ denotes binding
T359 1289-1297 NN denotes activity
T360 1298-1300 IN denotes of
T361 1301-1305 NNP denotes CREB
T362 1305-1306 . denotes .
T363 1307-1312 NNS denotes Cells
T364 1313-1326 RB denotes concomitantly
T365 1327-1334 VBN denotes treated
T366 1335-1339 IN denotes with
T367 1340-1343 NNP denotes PTX
T368 1344-1347 CC denotes and
T369 1348-1351 NNP denotes LPS
T370 1352-1360 VBD denotes secreted
T371 1361-1368 JJ denotes similar
T372 1369-1375 NNS denotes levels
T373 1376-1378 IN denotes of
T374 1379-1384 NNP denotes TNF-α
T375 1385-1387 IN denotes in
T376 1388-1391 DT denotes the
T377 1392-1400 NN denotes presence
T378 1401-1404 CC denotes and
T379 1405-1412 NN denotes absence
T380 1413-1420 NNP denotes Protein
T381 1421-1427 NN denotes kinase
T382 1428-1429 DT denotes A
T383 1430-1440 NN denotes inhibition
T384 1440-1441 . denotes .
T385 1443-1453 NNP denotes DISCUSSION
T386 1454-1457 NNP denotes The
T387 1458-1467 VBD denotes increased
T388 1468-1473 NN denotes level
T389 1474-1476 IN denotes of
T390 1477-1481 NNP denotes cAMP
T391 1482-1486 WDT denotes that
T392 1487-1494 VBZ denotes results
T393 1495-1499 IN denotes from
T394 1500-1517 NN denotes phosphodiesterase
T395 1518-1528 NN denotes inhibition
T396 1529-1536 VBZ denotes affects
T397 1537-1548 JJ denotes cytoplasmic
T398 1549-1552 CC denotes and
T399 1553-1560 JJ denotes nuclear
T400 1561-1567 NNS denotes events
T401 1567-1568 , denotes ,
T402 1569-1578 VBG denotes resulting
T403 1579-1581 IN denotes in
T404 1582-1585 DT denotes the
T405 1586-1597 NN denotes attenuation
T406 1598-1600 IN denotes of
T407 1601-1606 NNP denotes NF-κB
T408 1607-1610 CC denotes and
T409 1611-1614 DT denotes the
T410 1615-1625 NN denotes activation
T411 1626-1628 IN denotes of
T412 1629-1633 NNP denotes CREB
T413 1634-1649 JJ denotes transcriptional
T414 1650-1653 NNP denotes DNA
T415 1654-1661 JJ denotes binding
T416 1662-1669 IN denotes through
T417 1670-1678 NNS denotes pathways
T418 1679-1683 WDT denotes that
T419 1684-1687 VBP denotes are
T420 1688-1697 RB denotes partially
T421 1698-1705 NNP denotes Protein
T422 1706-1712 NN denotes kinase
T423 1713-1726 NN denotes A-independent
T424 1726-1727 . denotes .
T425 1729-1739 NNP denotes CONCLUSION
T426 1740-1752 JJ denotes PTX-mediated
T427 1753-1770 NN denotes phosphodiesterase
T428 1771-1781 NN denotes inhibition
T429 1782-1788 VBZ denotes occurs
T430 1789-1798 RB denotes partially
T431 1799-1806 IN denotes through
T432 1807-1808 DT denotes a
T433 1809-1816 NNP denotes Protein
T434 1817-1823 NN denotes kinase
T435 1824-1837 JJ denotes A-independent
T436 1838-1845 NN denotes pathway
T437 1846-1849 CC denotes and
T438 1850-1853 MD denotes may
T439 1854-1859 VB denotes serve
T440 1860-1862 IN denotes as
T441 1863-1864 DT denotes a
T442 1865-1871 JJ denotes useful
T443 1872-1876 NN denotes tool
T444 1877-1879 IN denotes in
T445 1880-1883 DT denotes the
T446 1884-1895 NN denotes attenuation
T447 1896-1898 IN denotes of
T448 1899-1910 JJ denotes LPS-induced
T449 1911-1923 NN denotes inflammation
T450 1923-1924 . denotes .
T1162 1940-1943 DT denotes The
T1163 1944-1953 JJ denotes bacterial
T1164 1954-1962 NN denotes membrane
T1165 1963-1972 NN denotes component
T1166 1973-1991 NN denotes lipopolysaccharide
T1167 1992-1993 -LRB- denotes (
T1168 1993-1996 NNP denotes LPS
T1169 1996-1997 -RRB- denotes )
T1170 1998-2000 VBZ denotes is
T1171 2001-2008 JJ denotes capable
T1172 2009-2011 IN denotes of
T1173 2012-2022 VBG denotes initiating
T1174 2023-2038 NN denotes phosphorylation
T1175 2039-2042 CC denotes and
T1176 2043-2053 NN denotes activation
T1177 2054-2056 IN denotes of
T1178 2057-2065 JJ denotes multiple
T1179 2066-2070 NN denotes host
T1180 2071-2084 JJ denotes intracellular
T1181 2085-2092 NN denotes protein
T1182 2093-2100 NNS denotes kinases
T1183 2101-2104 CC denotes and
T1184 2105-2118 NN denotes transcription
T1185 2119-2126 NNS denotes factors
T1186 2126-2127 . denotes .
T1187 2128-2141 NNP denotes Transcription
T1188 2142-2148 NN denotes factor
T1189 2149-2159 NN denotes activation
T1190 2159-2160 , denotes ,
T1191 2161-2166 WDT denotes which
T1192 2167-2174 VBZ denotes results
T1193 2175-2177 IN denotes in
T1194 2178-2181 DT denotes the
T1195 2182-2192 NN denotes modulation
T1196 2193-2195 IN denotes of
T1197 2196-2200 NN denotes gene
T1198 2201-2214 NN denotes transcription
T1199 2215-2218 CC denotes and
T1200 2219-2226 NN denotes protein
T1201 2227-2236 NN denotes synthesis
T1202 2236-2237 , denotes ,
T1203 2238-2240 VBZ denotes is
T1204 2241-2242 DT denotes a
T1205 2243-2251 JJ denotes critical
T1206 2252-2259 NN denotes element
T1207 2260-2262 IN denotes in
T1208 2263-2266 DT denotes the
T1209 2267-2274 NN denotes defense
T1210 2275-2284 NN denotes mechanism
T1211 2285-2287 IN denotes of
T1212 2288-2291 DT denotes the
T1213 2292-2296 NN denotes host
T1214 2297-2303 JJ denotes immune
T1215 2304-2310 NN denotes system
T1216 2310-2314 CD denotes .1,2
T1217 2315-2326 JJ denotes LPS-induced
T1218 2327-2340 NN denotes transcription
T1219 2341-2347 NN denotes factor
T1220 2348-2358 NN denotes activation
T1221 2359-2362 VBZ denotes has
T1222 2363-2367 VBN denotes been
T1223 2368-2373 VBN denotes shown
T1224 2374-2376 TO denotes to
T1225 2377-2379 VB denotes be
T1226 2380-2381 DT denotes a
T1227 2382-2385 JJ denotes key
T1228 2386-2395 NN denotes regulator
T1229 2396-2398 IN denotes of
T1230 2399-2404 NN denotes tumor
T1231 2405-2413 NN denotes necrosis
T1232 2414-2422 NN denotes factor-α
T1233 2423-2424 -LRB- denotes (
T1234 2424-2429 NNP denotes TNF-α
T1235 2429-2430 -RRB- denotes )
T1236 2431-2441 NN denotes production
T1237 2441-2443 CD denotes .3
T1238 2444-2449 NNP denotes TNF-α
T1239 2450-2452 VBZ denotes is
T1240 2453-2454 DT denotes a
T1241 2455-2461 JJ denotes potent
T1242 2462-2478 JJ denotes pro-inflammatory
T1243 2479-2487 NN denotes cytokine
T1244 2488-2496 VBN denotes involved
T1245 2497-2499 IN denotes in
T1246 2500-2501 DT denotes a
T1247 2502-2506 JJ denotes wide
T1248 2507-2515 NN denotes spectrum
T1249 2516-2518 IN denotes of
T1250 2519-2527 JJ denotes cellular
T1251 2528-2537 NNS denotes responses
T1252 2537-2538 . denotes .
T1253 2539-2550 RB denotes Furthermore
T1254 2550-2551 , denotes ,
T1255 2552-2557 JJ denotes TNF-α
T1256 2558-2567 NN denotes synthesis
T1257 2568-2571 MD denotes can
T1258 2572-2574 VB denotes be
T1259 2575-2585 VBN denotes attenuated
T1260 2586-2588 IN denotes in
T1261 2589-2595 JJ denotes immune
T1262 2596-2601 NNS denotes cells
T1263 2602-2609 VBN denotes exposed
T1264 2610-2612 TO denotes to
T1265 2613-2630 VB denotes phosphodiesterase
T1266 2631-2632 -LRB- denotes (
T1267 2632-2635 NNP denotes PDE
T1268 2635-2636 -RRB- denotes )
T1269 2637-2647 NN denotes inhibition
T1270 2648-2653 IN denotes after
T1271 2654-2663 NN denotes challenge
T1272 2664-2666 IN denotes by
T1273 2667-2668 DT denotes a
T1274 2669-2676 NN denotes variety
T1275 2677-2679 IN denotes of
T1276 2680-2696 JJ denotes pro-inflammatory
T1277 2697-2707 NNS denotes stimulants
T1278 2707-2709 CD denotes .4
T1279 2710-2713 DT denotes The
T1280 2714-2723 VBG denotes signaling
T1281 2724-2734 NNS denotes mechanisms
T1282 2735-2743 VBN denotes affected
T1283 2744-2746 IN denotes by
T1284 2747-2750 NNP denotes PDE
T1285 2751-2761 NN denotes inhibition
T1286 2761-2762 , denotes ,
T1287 2763-2768 WDT denotes which
T1288 2769-2779 RB denotes ultimately
T1289 2780-2784 VBP denotes lead
T1290 2785-2787 TO denotes to
T1291 2788-2791 DT denotes the
T1292 2792-2806 NN denotes downregulation
T1293 2807-2809 IN denotes of
T1294 2810-2815 JJ denotes TNF-α
T1295 2816-2826 NN denotes production
T1296 2826-2827 , denotes ,
T1297 2828-2832 VBP denotes have
T1298 2833-2836 RB denotes not
T1299 2837-2841 VBN denotes been
T1300 2842-2846 RB denotes well
T1301 2847-2860 VBN denotes characterized
T1302 2861-2863 IN denotes in
T1303 2864-2876 JJ denotes inflammatory
T1304 2877-2882 NNS denotes cells
T1305 2882-2883 . denotes .
T1306 2884-2895 NNP denotes Classically
T1307 2895-2896 , denotes ,
T1308 2897-2899 PRP denotes it
T1309 2900-2903 VBZ denotes has
T1310 2904-2908 VBN denotes been
T1311 2909-2921 VBN denotes demonstrated
T1312 2922-2926 IN denotes that
T1313 2927-2930 NNP denotes PDE
T1314 2931-2941 NN denotes inhibition
T1315 2942-2949 NNS denotes results
T1316 2950-2952 IN denotes in
T1317 2953-2956 DT denotes the
T1318 2957-2970 JJ denotes intracellular
T1319 2971-2983 NN denotes accumulation
T1320 2984-2986 IN denotes of
T1321 2987-2990 DT denotes the
T1322 2991-2997 JJ denotes second
T1323 2998-3007 NN denotes messenger
T1324 3008-3014 JJ denotes cyclic
T1325 3015-3026 JJ denotes adenosine-3
T1326 3026-3028 SYM denotes ,5
T1327 3028-3029 : denotes -
T1328 3029-3042 NN denotes monophosphate
T1329 3043-3044 -LRB- denotes (
T1330 3044-3048 NNP denotes cAMP
T1331 3048-3049 -RRB- denotes )
T1332 3050-3053 CC denotes and
T1333 3054-3064 JJ denotes subsequent
T1334 3065-3075 NN denotes activation
T1335 3076-3078 IN denotes of
T1336 3079-3086 NNP denotes Protein
T1337 3087-3093 VBP denotes kinase
T1338 3094-3095 DT denotes A
T1339 3096-3097 -LRB- denotes (
T1340 3097-3100 NNP denotes PKA
T1341 3100-3101 -RRB- denotes )
T1342 3101-3103 CD denotes .5
T1343 3104-3107 NNP denotes PKA
T1344 3108-3118 NN denotes activation
T1345 3119-3123 RB denotes then
T1346 3124-3129 VBZ denotes leads
T1347 3130-3132 TO denotes to
T1348 3133-3136 DT denotes the
T1349 3137-3152 NN denotes phosphorylation
T1350 3153-3155 IN denotes of
T1351 3156-3159 DT denotes the
T1352 3160-3173 NN denotes transcription
T1353 3174-3180 NN denotes factor
T1354 3181-3194 JJ denotes cAMP-response
T1355 3195-3202 NN denotes element
T1356 3203-3210 JJ denotes binding
T1357 3211-3218 NN denotes protein
T1358 3219-3220 -LRB- denotes (
T1359 3220-3224 NNP denotes CREB
T1360 3224-3225 -RRB- denotes )
T1361 3225-3226 , denotes ,
T1362 3227-3239 NN denotes transmission
T1363 3240-3242 IN denotes of
T1364 3243-3250 NNS denotes signals
T1365 3251-3255 IN denotes into
T1366 3256-3259 DT denotes the
T1367 3260-3267 NN denotes nucleus
T1368 3267-3268 , denotes ,
T1369 3269-3272 CC denotes and
T1370 3273-3276 DT denotes the
T1371 3277-3287 JJ denotes subsequent
T1372 3288-3298 NN denotes modulation
T1373 3299-3301 IN denotes of
T1374 3302-3306 NN denotes gene
T1375 3307-3320 NN denotes transcription
T1376 3320-3322 CD denotes .6
T1377 3323-3327 DT denotes This
T1378 3328-3338 RB denotes apparently
T1379 3339-3345 JJ denotes simple
T1380 3346-3352 JJ denotes linear
T1381 3353-3360 NN denotes cascade
T1382 3361-3365 VBZ denotes does
T1383 3366-3369 RB denotes not
T1384 3370-3375 RB denotes fully
T1385 3376-3383 VB denotes explain
T1386 3384-3387 DT denotes the
T1387 3388-3397 NN denotes mechanism
T1388 3398-3400 IN denotes by
T1389 3401-3406 WDT denotes which
T1390 3407-3409 DT denotes an
T1391 3410-3419 NN denotes elevation
T1392 3420-3422 IN denotes in
T1393 3423-3426 DT denotes the
T1394 3427-3440 JJ denotes intracellular
T1395 3441-3445 NNP denotes cAMP
T1396 3446-3451 NN denotes level
T1397 3452-3458 VBZ denotes exerts
T1398 3459-3471 JJ denotes wide-ranging
T1399 3472-3479 NNS denotes effects
T1400 3480-3482 IN denotes on
T1401 3483-3491 JJ denotes multiple
T1402 3492-3500 JJ denotes cellular
T1403 3501-3510 NNS denotes functions
T1404 3510-3511 . denotes .
T1405 3512-3517 EX denotes There
T1406 3518-3520 VBZ denotes is
T1407 3521-3522 DT denotes a
T1408 3523-3530 VBG denotes growing
T1409 3531-3535 NN denotes body
T1410 3536-3538 IN denotes of
T1411 3539-3547 NN denotes evidence
T1412 3548-3558 VBG denotes suggesting
T1413 3559-3563 IN denotes that
T1414 3564-3568 NNP denotes cAMP
T1415 3569-3572 MD denotes may
T1416 3573-3581 VB denotes function
T1417 3582-3589 IN denotes through
T1418 3590-3594 DT denotes both
T1419 3595-3608 JJ denotes PKA-dependent
T1420 3609-3612 CC denotes and
T1421 3613-3614 : denotes -
T1422 3614-3625 JJ denotes independent
T1423 3626-3636 NNS denotes mechanisms
T1424 3636-3638 CD denotes .6
T1425 3639-3640 CD denotes 8
T1426 3641-3652 JJ denotes LPS-induced
T1427 3653-3663 NN denotes activation
T1428 3664-3666 IN denotes of
T1429 3667-3670 DT denotes the
T1430 3671-3684 NN denotes transcription
T1431 3685-3691 NN denotes factor
T1432 3692-3699 JJ denotes nuclear
T1433 3700-3709 NNP denotes factor-κB
T1434 3710-3711 -LRB- denotes (
T1435 3711-3716 NNP denotes NF-κB
T1436 3716-3717 -RRB- denotes )
T1437 3718-3721 VBZ denotes has
T1438 3722-3726 RB denotes also
T1439 3727-3731 VBN denotes been
T1440 3732-3735 DT denotes the
T1441 3736-3741 NN denotes focus
T1442 3742-3744 IN denotes of
T1443 3745-3746 DT denotes a
T1444 3747-3752 JJ denotes great
T1445 3753-3757 NN denotes deal
T1446 3758-3760 IN denotes of
T1447 3761-3769 NN denotes research
T1448 3769-3770 . denotes .
T1449 3771-3773 PRP denotes It
T1450 3774-3777 VBZ denotes has
T1451 3778-3782 VBN denotes been
T1452 3783-3790 RB denotes clearly
T1453 3791-3803 VBN denotes demonstrated
T1454 3804-3808 IN denotes that
T1455 3809-3815 NNS denotes agents
T1456 3816-3820 WDT denotes that
T1457 3821-3829 VBP denotes increase
T1458 3830-3843 JJ denotes intracellular
T1459 3844-3848 NNP denotes cAMP
T1460 3849-3853 RB denotes also
T1461 3854-3861 VBP denotes inhibit
T1462 3862-3877 JJ denotes NF-κB-dependent
T1463 3878-3894 JJ denotes pro-inflammatory
T1464 3895-3899 NN denotes gene
T1465 3900-3913 NN denotes transcription
T1466 3913-3914 , denotes ,
T1467 3915-3927 RB denotes particularly
T1468 3928-3930 IN denotes of
T1469 3931-3934 DT denotes the
T1470 3935-3940 NNP denotes TNF-α
T1471 3941-3945 NN denotes gene
T1472 3945-3947 CD denotes .9
T1473 3948-3959 NNP denotes Controversy
T1474 3960-3966 VBZ denotes exists
T1475 3967-3976 VBG denotes regarding
T1476 3977-3980 DT denotes the
T1477 3981-3986 JJ denotes exact
T1478 3987-3996 NN denotes mechanism
T1479 3996-3997 -LRB- denotes (
T1480 3997-3998 PRP denotes s
T1481 3998-3999 -RRB- denotes )
T1482 4000-4002 IN denotes by
T1483 4003-4008 WDT denotes which
T1484 4009-4012 NNP denotes PDE
T1485 4013-4023 NN denotes inhibition
T1486 4024-4038 VBZ denotes down-regulates
T1487 4039-4044 JJ denotes TNF-α
T1488 4045-4055 NN denotes production
T1489 4055-4056 . denotes .
T1490 4057-4070 NNS denotes Possibilities
T1491 4071-4078 VBP denotes include
T1492 4078-4079 , denotes ,
T1493 4080-4083 CC denotes but
T1494 4084-4087 VBP denotes are
T1495 4088-4091 RB denotes not
T1496 4092-4099 VBN denotes limited
T1497 4100-4102 TO denotes to
T1498 4102-4103 , denotes ,
T1499 4104-4114 NN denotes inhibition
T1500 4115-4117 IN denotes of
T1501 4118-4123 NNP denotes NF-κB
T1502 4124-4127 NNP denotes DNA
T1503 4128-4135 JJ denotes binding
T1504 4136-4144 NN denotes activity
T1505 4144-4145 , denotes ,
T1506 4146-4160 NN denotes downregulation
T1507 4161-4163 IN denotes of
T1508 4164-4169 JJ denotes NF-κB
T1509 4170-4185 JJ denotes transcriptional
T1510 4186-4194 NN denotes activity
T1511 4194-4195 , denotes ,
T1512 4196-4205 VBD denotes increased
T1513 4206-4210 NNP denotes CREB
T1514 4211-4221 NN denotes activation
T1515 4221-4222 , denotes ,
T1516 4223-4226 CC denotes and
T1517 4227-4238 NN denotes competition
T1518 4239-4246 IN denotes between
T1519 4247-4252 NNP denotes NF-κB
T1520 4253-4256 CC denotes and
T1521 4257-4261 NNP denotes CREB
T1522 4262-4265 IN denotes for
T1523 4266-4272 JJ denotes common
T1524 4273-4286 NNS denotes co-activators
T1525 4287-4291 JJ denotes such
T1526 4292-4294 IN denotes as
T1527 4295-4299 NNP denotes CREB
T1528 4300-4307 JJ denotes binding
T1529 4308-4315 NN denotes protein
T1530 4316-4317 -LRB- denotes (
T1531 4317-4320 NNP denotes CBP
T1532 4320-4321 -RRB- denotes )
T1533 4321-4322 . denotes .
T1534 4323-4325 PRP denotes It
T1535 4326-4328 VBZ denotes is
T1536 4329-4333 RB denotes also
T1537 4334-4337 RB denotes not
T1538 4338-4343 VBN denotes known
T1539 4344-4351 IN denotes whether
T1540 4352-4357 DT denotes these
T1541 4358-4367 NNS denotes processes
T1542 4368-4372 VBP denotes rely
T1543 4373-4379 RB denotes solely
T1544 4380-4384 IN denotes upon
T1545 4385-4388 DT denotes the
T1546 4389-4399 NN denotes activation
T1547 4400-4402 IN denotes of
T1548 4403-4406 NNP denotes PKA
T1549 4406-4407 . denotes .
T1550 4408-4417 RB denotes Therefore
T1551 4417-4418 , denotes ,
T1552 4419-4422 DT denotes the
T1553 4423-4432 NN denotes objective
T1554 4433-4435 IN denotes of
T1555 4436-4439 DT denotes the
T1556 4440-4447 JJ denotes present
T1557 4448-4453 NN denotes study
T1558 4454-4456 VBZ denotes is
T1559 4457-4459 TO denotes to
T1560 4460-4469 VB denotes determine
T1561 4470-4473 DT denotes the
T1562 4474-4481 NNS denotes effects
T1563 4482-4484 IN denotes of
T1564 4485-4496 JJ denotes nonspecific
T1565 4497-4500 NNP denotes PDE
T1566 4501-4511 NN denotes inhibition
T1567 4512-4516 IN denotes with
T1568 4517-4518 LS denotes 1
T1569 4518-4519 : denotes -
T1570 4519-4520 NNP denotes [
T1571 4520-4530 JJ denotes 5-oxohexyl
T1572 4530-4531 NNP denotes ]
T1573 4531-4535 CD denotes -3,7
T1574 4535-4536 : denotes -
T1575 4536-4552 NN denotes dimethylxanthine
T1576 4553-4554 -LRB- denotes (
T1577 4554-4568 NNP denotes Pentoxifylline
T1578 4568-4569 : denotes ;
T1579 4570-4573 NNP denotes PTX
T1580 4573-4574 -RRB- denotes )
T1581 4575-4577 IN denotes on
T1582 4578-4583 NN denotes NF-κB
T1583 4584-4587 CC denotes and
T1584 4588-4592 NNP denotes CREB
T1585 4593-4603 NN denotes activation
T1586 4604-4606 IN denotes in
T1587 4607-4612 NN denotes vitro
T1588 4613-4615 IN denotes in
T1589 4616-4621 JJ denotes human
T1590 4622-4633 NN denotes mononuclear
T1591 4634-4639 NNS denotes cells
T1592 4639-4640 . denotes .
T1593 4641-4645 IN denotes With
T1594 4646-4649 DT denotes the
T1595 4650-4653 NN denotes use
T1596 4654-4656 IN denotes of
T1597 4657-4665 JJ denotes specific
T1598 4666-4676 NNS denotes inhibitors
T1599 4676-4677 , denotes ,
T1600 4678-4680 PRP denotes we
T1601 4681-4685 RB denotes also
T1602 4686-4698 VBD denotes investigated
T1603 4699-4702 DT denotes the
T1604 4703-4707 NN denotes role
T1605 4708-4710 IN denotes of
T1606 4711-4714 NNP denotes PKA
T1607 4715-4717 IN denotes in
T1608 4718-4729 JJ denotes LPS-induced
T1609 4730-4735 JJ denotes TNF-α
T1610 4736-4746 NN denotes production
T1611 4746-4747 . denotes .
T2464 0-4 DT denotes this
T2465 5-10 NN denotes study
T2466 11-14 VBD denotes was
T2467 4786-4794 VBN denotes approved
T2468 4795-4797 IN denotes by
T2469 4798-4801 DT denotes the
T2470 4802-4807 NNP denotes Human
T2471 4808-4816 NNP denotes Research
T2472 4817-4828 NNPS denotes Protections
T2473 4829-4836 NNP denotes Program
T2474 4837-4840 CC denotes and
T2475 4841-4844 DT denotes the
T2476 4845-4858 JJ denotes Institutional
T2477 4859-4865 NNP denotes Review
T2478 4866-4871 NNP denotes Board
T2479 4871-4872 . denotes .
T2480 4873-4880 VBN denotes Written
T2481 4881-4888 NN denotes consent
T2482 4889-4891 TO denotes to
T2483 4892-4903 VB denotes participate
T2484 4904-4906 IN denotes in
T2485 4907-4910 DT denotes the
T2486 4911-4916 NN denotes study
T2487 4917-4920 VBD denotes was
T2488 4921-4929 VBN denotes obtained
T2489 4930-4934 IN denotes from
T2490 4935-4938 DT denotes all
T2491 4939-4949 NNS denotes volunteers
T2492 4950-4955 RB denotes prior
T2493 4956-4958 TO denotes to
T2494 4959-4964 NN denotes blood
T2495 4965-4986 VBN denotes donation. Heparinized
T2496 4987-4998 NNS denotes Vacutainers
T2497 4999-5003 VBD denotes were
T2498 5004-5013 VBN denotes purchased
T2499 5014-5018 IN denotes from
T2500 5019-5025 NNP denotes Becton
T2501 5026-5035 NNP denotes Dickinson
T2502 5036-5037 -LRB- denotes (
T2503 5037-5040 NNP denotes San
T2504 5041-5045 NNP denotes Jose
T2505 5045-5046 , denotes ,
T2506 5047-5049 NNP denotes CA
T2507 5049-5050 -RRB- denotes )
T2508 5050-5051 . denotes .
T152 0-4 DT denotes this
T153 5-10 NN denotes study
T154 11-14 VBD denotes was
T155 15-17 TO denotes to
T156 18-27 VB denotes determine
T157 28-31 DT denotes the
T158 32-38 NN denotes effect
T159 39-41 IN denotes of
T160 42-53 JJ denotes nonspecific
T161 54-71 NN denotes phosphodiesterase
R78 T180 T162 punct -,inhibition
R79 T181 T154 conj stimulated,was
R80 T182 T184 amod human,cells
R81 T183 T184 compound mononuclear,cells
R82 T184 T181 dobj cells,stimulated
R83 T185 T154 punct .,was
R84 T186 T194 advmod INTRODUCTION,is
R85 T187 T188 det The,production
R86 T188 T194 nsubj production,is
R87 T189 T188 prep of,production
R88 T190 T189 pobj TNF-α,of
R89 T191 T188 prep following,production
R90 T192 T193 compound LPS,stimulation
R91 T193 T191 pobj stimulation,following
R92 T194 T194 ROOT is,is
R93 T195 T194 attr one,is
R94 T196 T195 prep of,one
R95 T197 T199 det the,steps
R96 T198 T199 amod key,steps
R97 T199 T196 pobj steps,of
R98 T200 T199 prep in,steps
R99 T201 T202 amod bacterial,sepsis
R103 T205 T194 punct .,is
R104 T206 T207 det The,mechanism
R105 T207 T220 nsubj mechanism,remains
R106 T208 T212 prep by,alters
R107 T209 T208 pobj which,by
R108 T210 T211 amod phosphodiesterase,inhibition
R109 T211 T212 nsubj inhibition,alters
R110 T212 T207 relcl alters,mechanism
R111 T213 T214 amod TNF-α,production
R112 T214 T212 dobj production,alters
R113 T215 T212 prep in,alters
R114 T216 T217 det the,presence
R115 T217 T215 pobj presence,in
R116 T218 T217 prep of,presence
R117 T219 T218 pobj LPS,of
R118 T220 T220 ROOT remains,remains
R119 T221 T220 acomp unclear,remains
R120 T222 T220 punct .,remains
R121 T223 T226 compound METHODS,cells
R122 T224 T226 compound Human,cells
R123 T225 T226 compound mononuclear,cells
R124 T226 T228 nsubjpass cells,stimulated
R125 T227 T228 auxpass were,stimulated
R126 T228 T249 ccomp stimulated,mM
R127 T229 T228 prep with,stimulated
R128 T230 T229 pobj LPS,with
R129 T231 T235 punct (,mL
R130 T232 T233 nummod 1,μg
R131 T233 T235 compound μg,mL
R132 T234 T235 compound /,mL
R133 T235 T230 appos mL,LPS
R134 T236 T235 punct ),mL
R135 T237 T230 punct ",",LPS
R136 T238 T228 prep in,stimulated
R137 T239 T240 det the,presence
R138 T240 T238 pobj presence,in
R139 T241 T240 cc and,presence
R140 T242 T240 conj absence,presence
R141 T243 T242 prep of,absence
R142 T244 T243 pobj Pentoxifylline,of
R143 T245 T246 punct (,PTX
R144 T246 T244 appos PTX,Pentoxifylline
R145 T247 T249 punct ;,mM
R146 T248 T249 nummod 20,mM
R147 T249 T249 ROOT mM,mM
R148 T250 T249 punct ),mM
R149 T251 T249 punct ",",mM
R150 T252 T255 det a,inhibitor
R151 T253 T255 amod nonspecific,inhibitor
R152 T254 T255 compound phosphodiesterase,inhibitor
R153 T255 T249 appos inhibitor,mM
R154 T256 T249 punct .,mM
R155 T257 T258 amod Western,blotting
R156 T258 T281 nsubjpass blotting,performed
R157 T259 T258 prep of,blotting
R158 T260 T262 amod phosphorylated,I-κBα
R159 T261 T262 compound cytoplasmic,I-κBα
R160 T262 T259 pobj I-κBα,of
R161 T263 T262 punct ",",I-κBα
R162 T264 T266 amod nuclear,p65
R163 T265 T266 compound factor-κB,p65
R164 T266 T262 appos p65,I-κBα
R165 T267 T266 punct (,p65
R166 T268 T266 appos NF-κB,p65
R167 T269 T266 punct ),p65
R168 T270 T266 punct ",",p65
R169 T271 T266 cc and,p65
R170 T272 T274 amod nuclear,element
R171 T273 T274 amod cAMP-response,element
R172 T274 T276 compound element,protein
R173 T275 T276 amod binding,protein
R174 T276 T266 conj protein,p65
R175 T277 T278 punct (,CREB
R176 T278 T276 appos CREB,protein
R177 T279 T276 punct ),protein
R178 T280 T281 auxpass was,performed
R179 T281 T281 ROOT performed,performed
R180 T282 T281 punct .,performed
R181 T283 T284 npadvmod DNA,binding
R182 T284 T290 nsubjpass binding,verified
R183 T285 T284 prep of,binding
R184 T286 T285 pobj NF-κB,of
R185 T287 T286 cc and,NF-κB
R186 T288 T286 conj CREB,NF-κB
R187 T289 T290 auxpass was,verified
R188 T290 T290 ROOT verified,verified
R189 T291 T290 agent by,verified
R190 T292 T295 amod electrophoretic,assay
R191 T293 T294 compound mobility,shift
R192 T294 T295 compound shift,assay
R193 T295 T291 pobj assay,by
R194 T296 T290 punct .,verified
R195 T297 T298 amod TNF-α,levels
R196 T298 T300 nsubjpass levels,determined
R197 T299 T300 auxpass were,determined
R198 T300 T300 ROOT determined,determined
R199 T301 T300 prep in,determined
R200 T302 T303 det the,supernatant
R201 T303 T301 pobj supernatant,in
R202 T304 T303 prep of,supernatant
R203 T305 T306 amod stimulated,cells
R204 T306 T304 pobj cells,of
R205 T307 T303 prep in,supernatant
R206 T308 T309 det the,presence
R207 T309 T307 pobj presence,in
R208 T310 T309 cc and,presence
R209 T311 T309 conj absence,presence
R210 T312 T313 compound Protein,kinase
R211 T313 T313 ROOT kinase,kinase
R212 T314 T315 det A,inhibition
R213 T315 T315 ROOT inhibition,inhibition
R214 T316 T315 prep by,inhibition
R215 T317 T320 det an,assay
R216 T318 T320 nmod enzyme-linked,assay
R217 T319 T320 compound immunosorbent,assay
R218 T320 T316 pobj assay,by
R219 T321 T320 punct (,assay
R220 T322 T320 appos ELISA,assay
R221 T323 T320 punct ),assay
R222 T324 T315 punct .,inhibition
R223 T325 T326 compound RESULTS,PTX
R224 T326 T328 nsubjpass PTX,demonstrated
R225 T327 T328 auxpass was,demonstrated
R226 T328 T328 ROOT demonstrated,demonstrated
R227 T329 T331 aux to,reduce
R228 T330 T331 advmod significantly,reduce
R229 T331 T328 xcomp reduce,demonstrated
R230 T332 T334 amod cytoplasmic,phosphorylation
R231 T333 T334 amod I-κBα,phosphorylation
R232 T334 T331 dobj phosphorylation,reduce
R233 T335 T334 punct ",",phosphorylation
R234 T336 T337 amod nuclear,p65
R235 T337 T338 compound p65,phosphorylation
R236 T338 T334 appos phosphorylation,phosphorylation
R237 T339 T338 punct ",",phosphorylation
R238 T340 T338 cc and,phosphorylation
R239 T341 T344 det the,activity
R240 T342 T344 nmod DNA,activity
R241 T343 T344 amod binding,activity
R242 T344 T338 conj activity,phosphorylation
R243 T345 T344 prep of,activity
R244 T346 T345 pobj NF-κB,of
R245 T347 T328 punct .,demonstrated
R246 T348 T353 prep In,enhanced
R247 T349 T348 pobj contrast,In
R248 T350 T353 punct ",",enhanced
R249 T351 T353 nsubj PTX,enhanced
R250 T352 T353 advmod markedly,enhanced
R251 T353 T353 ROOT enhanced,enhanced
R252 T354 T355 det the,phosphorylation
R253 T355 T353 dobj phosphorylation,enhanced
R254 T356 T355 cc and,phosphorylation
R255 T357 T359 amod DNA,activity
R256 T358 T359 amod binding,activity
R257 T359 T355 conj activity,phosphorylation
R258 T360 T355 prep of,phosphorylation
R259 T361 T360 pobj CREB,of
R260 T362 T353 punct .,enhanced
R261 T363 T370 nsubj Cells,secreted
R262 T364 T365 advmod concomitantly,treated
R263 T365 T363 acl treated,Cells
R264 T366 T365 prep with,treated
R265 T367 T366 pobj PTX,with
R266 T368 T367 cc and,PTX
R267 T369 T367 conj LPS,PTX
R268 T370 T370 ROOT secreted,secreted
R269 T371 T372 amod similar,levels
R270 T372 T370 dobj levels,secreted
R271 T373 T372 prep of,levels
R272 T374 T373 pobj TNF-α,of
R273 T375 T370 prep in,secreted
R274 T376 T377 det the,presence
R275 T377 T375 pobj presence,in
R276 T378 T377 cc and,presence
R277 T379 T377 conj absence,presence
R278 T380 T381 compound Protein,kinase
R279 T381 T381 ROOT kinase,kinase
R280 T382 T383 det A,inhibition
R281 T383 T383 ROOT inhibition,inhibition
R282 T384 T383 punct .,inhibition
R283 T385 T396 nsubj DISCUSSION,affects
R284 T386 T388 det The,level
R285 T387 T388 amod increased,level
R286 T388 T396 nsubj level,affects
R287 T389 T388 prep of,level
R288 T390 T389 pobj cAMP,of
R289 T391 T392 nsubj that,results
R290 T392 T388 relcl results,level
R291 T393 T392 prep from,results
R292 T394 T395 amod phosphodiesterase,inhibition
R293 T395 T393 pobj inhibition,from
R294 T396 T396 ROOT affects,affects
R295 T397 T400 amod cytoplasmic,events
R296 T398 T397 cc and,cytoplasmic
R297 T399 T397 conj nuclear,cytoplasmic
R298 T400 T396 dobj events,affects
R299 T401 T396 punct ",",affects
R300 T402 T396 advcl resulting,affects
R301 T403 T402 prep in,resulting
R302 T404 T405 det the,attenuation
R303 T405 T403 pobj attenuation,in
R304 T406 T405 prep of,attenuation
R305 T407 T406 pobj NF-κB,of
R306 T408 T405 cc and,attenuation
R307 T409 T410 det the,activation
R308 T410 T405 conj activation,attenuation
R309 T411 T410 prep of,activation
R310 T412 T414 compound CREB,DNA
R311 T413 T414 compound transcriptional,DNA
R312 T414 T411 pobj DNA,of
R313 T415 T410 amod binding,activation
R314 T416 T415 prep through,binding
R315 T417 T416 pobj pathways,through
R316 T418 T419 nsubj that,are
R317 T419 T417 relcl are,pathways
R318 T420 T419 advmod partially,are
R319 T421 T423 compound Protein,A-independent
R320 T422 T423 compound kinase,A-independent
R321 T423 T419 attr A-independent,are
R322 T424 T396 punct .,affects
R323 T425 T428 nmod CONCLUSION,inhibition
R324 T426 T428 amod PTX-mediated,inhibition
R325 T427 T428 compound phosphodiesterase,inhibition
R326 T428 T429 nsubj inhibition,occurs
R327 T429 T429 ROOT occurs,occurs
R328 T430 T431 advmod partially,through
R329 T431 T429 prep through,occurs
R330 T432 T436 det a,pathway
R331 T433 T436 nmod Protein,pathway
R332 T434 T436 nmod kinase,pathway
R333 T435 T436 compound A-independent,pathway
R334 T436 T431 pobj pathway,through
R335 T437 T429 cc and,occurs
R336 T438 T439 aux may,serve
R337 T439 T429 conj serve,occurs
R338 T440 T439 prep as,serve
R348 T450 T429 punct .,occurs
R777 T152 T153 det this,study
R779 T154 T154 ROOT was,was
R780 T155 T156 aux to,determine
R781 T156 T154 xcomp determine,was
R782 T157 T158 det the,effect
R783 T158 T156 dobj effect,determine
R784 T159 T158 prep of,effect
R785 T160 T162 amod nonspecific,inhibition
R786 T161 T162 compound phosphodiesterase,inhibition
R848 T1162 T1165 det The,component
R849 T1163 T1165 amod bacterial,component
R850 T1164 T1165 compound membrane,component
R851 T1165 T1170 nsubj component,is
R852 T1166 T1170 nsubj lipopolysaccharide,is
R853 T1167 T1168 punct (,LPS
R854 T1168 T1166 appos LPS,lipopolysaccharide
R855 T1169 T1166 punct ),lipopolysaccharide
R856 T1170 T1170 ROOT is,is
R857 T1171 T1170 acomp capable,is
R858 T1172 T1171 prep of,capable
R859 T1173 T1172 pcomp initiating,of
R860 T1174 T1173 dobj phosphorylation,initiating
R861 T1175 T1174 cc and,phosphorylation
R862 T1176 T1174 conj activation,phosphorylation
R863 T1177 T1174 prep of,phosphorylation
R864 T1178 T1182 amod multiple,kinases
R865 T1179 T1182 nmod host,kinases
R866 T1180 T1182 amod intracellular,kinases
R867 T1181 T1182 compound protein,kinases
R868 T1182 T1177 pobj kinases,of
R869 T1183 T1182 cc and,kinases
R870 T1184 T1185 compound transcription,factors
R871 T1185 T1182 conj factors,kinases
R872 T1186 T1170 punct .,is
R873 T1187 T1188 compound Transcription,factor
R874 T1188 T1189 compound factor,activation
R875 T1189 T1203 nsubj activation,is
R876 T1190 T1189 punct ",",activation
R877 T1191 T1192 nsubj which,results
R878 T1192 T1189 relcl results,activation
R879 T1193 T1192 prep in,results
R880 T1194 T1195 det the,modulation
R881 T1195 T1193 pobj modulation,in
R882 T1196 T1195 prep of,modulation
R883 T1197 T1198 compound gene,transcription
R884 T1198 T1196 pobj transcription,of
R885 T1199 T1198 cc and,transcription
R886 T1200 T1201 compound protein,synthesis
R887 T1201 T1198 conj synthesis,transcription
R888 T1202 T1203 punct ",",is
R889 T1203 T1203 ROOT is,is
R890 T1204 T1206 det a,element
R891 T1205 T1206 amod critical,element
R892 T1206 T1203 attr element,is
R893 T1207 T1206 prep in,element
R894 T1208 T1210 det the,mechanism
R895 T1209 T1210 compound defense,mechanism
R896 T1210 T1207 pobj mechanism,in
R897 T1211 T1210 prep of,mechanism
R898 T1212 T1215 det the,system
R899 T1213 T1215 nmod host,system
R900 T1214 T1215 amod immune,system
R901 T1215 T1211 pobj system,of
R902 T1216 T1220 nummod ".1,2",activation
R903 T1217 T1220 amod LPS-induced,activation
R904 T1218 T1219 compound transcription,factor
R905 T1219 T1220 compound factor,activation
R906 T1220 T1223 nsubjpass activation,shown
R907 T1221 T1223 aux has,shown
R908 T1222 T1223 auxpass been,shown
R909 T1223 T1223 ROOT shown,shown
R910 T1224 T1225 aux to,be
R911 T1225 T1223 xcomp be,shown
R912 T1226 T1228 det a,regulator
R913 T1227 T1228 amod key,regulator
R914 T1228 T1225 attr regulator,be
R915 T1229 T1228 prep of,regulator
R916 T1230 T1231 compound tumor,necrosis
R917 T1231 T1232 compound necrosis,factor-α
R918 T1232 T1229 pobj factor-α,of
R919 T1233 T1234 punct (,TNF-α
R920 T1234 T1232 appos TNF-α,factor-α
R921 T1235 T1232 punct ),factor-α
R922 T1236 T1238 compound production,TNF-α
R923 T1237 T1238 nummod .3,TNF-α
R924 T1238 T1228 appos TNF-α,regulator
R938 T1252 T1203 punct .,is
R939 T1253 T1259 advmod Furthermore,attenuated
R940 T1254 T1259 punct ",",attenuated
R941 T1255 T1256 amod TNF-α,synthesis
R942 T1256 T1259 nsubjpass synthesis,attenuated
R943 T1257 T1259 aux can,attenuated
R944 T1258 T1259 auxpass be,attenuated
R945 T1259 T1259 ROOT attenuated,attenuated
R946 T1260 T1259 prep in,attenuated
R947 T1261 T1262 amod immune,cells
R948 T1262 T1260 pobj cells,in
R949 T1263 T1259 conj exposed,attenuated
R950 T1264 T1265 aux to,phosphodiesterase
R951 T1265 T1263 advcl phosphodiesterase,exposed
R952 T1266 T1267 punct (,PDE
R953 T1267 T1265 appos PDE,phosphodiesterase
R954 T1268 T1259 punct ),attenuated
R955 T1269 T1301 nsubjpass inhibition,characterized
R956 T1270 T1269 prep after,inhibition
R957 T1271 T1270 pobj challenge,after
R958 T1272 T1271 prep by,challenge
R959 T1273 T1274 det a,variety
R960 T1274 T1272 pobj variety,by
R961 T1275 T1274 prep of,variety
R962 T1276 T1277 amod pro-inflammatory,stimulants
R963 T1277 T1275 pobj stimulants,of
R964 T1278 T1271 nummod .4,challenge
R965 T1279 T1281 det The,mechanisms
R966 T1280 T1281 amod signaling,mechanisms
R967 T1281 T1301 nsubjpass mechanisms,characterized
R968 T1282 T1281 acl affected,mechanisms
R969 T1283 T1282 agent by,affected
R970 T1284 T1285 compound PDE,inhibition
R971 T1285 T1283 pobj inhibition,by
R972 T1286 T1285 punct ",",inhibition
R973 T1287 T1289 nsubj which,lead
R974 T1288 T1289 advmod ultimately,lead
R975 T1289 T1285 relcl lead,inhibition
R976 T1290 T1289 prep to,lead
R977 T1291 T1292 det the,downregulation
R978 T1292 T1290 pobj downregulation,to
R979 T1293 T1292 prep of,downregulation
R980 T1294 T1295 compound TNF-α,production
R981 T1295 T1293 pobj production,of
R982 T1296 T1301 punct ",",characterized
R983 T1297 T1301 aux have,characterized
R984 T1298 T1301 neg not,characterized
R985 T1299 T1301 auxpass been,characterized
R986 T1300 T1301 advmod well,characterized
R987 T1301 T1301 ROOT characterized,characterized
R988 T1302 T1301 prep in,characterized
R989 T1303 T1304 amod inflammatory,cells
R990 T1304 T1302 pobj cells,in
R991 T1305 T1301 punct .,characterized
R992 T1306 T1311 advmod Classically,demonstrated
R993 T1307 T1311 punct ",",demonstrated
R994 T1308 T1311 nsubjpass it,demonstrated
R995 T1309 T1311 aux has,demonstrated
R996 T1310 T1311 auxpass been,demonstrated
R997 T1311 T1311 ROOT demonstrated,demonstrated
R998 T1312 T1337 mark that,kinase
R999 T1313 T1315 compound PDE,results
R1000 T1314 T1315 compound inhibition,results
R1001 T1315 T1337 nsubj results,kinase
R1002 T1316 T1315 prep in,results
R1003 T1317 T1319 det the,accumulation
R1004 T1318 T1319 amod intracellular,accumulation
R1005 T1319 T1316 pobj accumulation,in
R1006 T1320 T1319 prep of,accumulation
R1007 T1321 T1323 det the,messenger
R1008 T1322 T1323 amod second,messenger
R1009 T1323 T1320 pobj messenger,of
R1010 T1324 T1328 nmod cyclic,monophosphate
R1011 T1325 T1328 amod adenosine-3,monophosphate
R1012 T1326 T1328 punct ",5",monophosphate
R1013 T1327 T1328 punct -,monophosphate
R1014 T1328 T1315 appos monophosphate,results
R1015 T1329 T1330 punct (,cAMP
R1016 T1330 T1328 appos cAMP,monophosphate
R1017 T1331 T1330 punct ),cAMP
R1018 T1332 T1328 cc and,monophosphate
R1019 T1333 T1334 amod subsequent,activation
R1020 T1334 T1328 conj activation,monophosphate
R1021 T1335 T1334 prep of,activation
R1022 T1336 T1335 pobj Protein,of
R1023 T1337 T1311 ccomp kinase,demonstrated
R1024 T1338 T1340 det A,PKA
R1025 T1339 T1340 punct (,PKA
R1026 T1340 T1337 appos PKA,kinase
R1027 T1341 T1340 punct ),PKA
R1028 T1342 T1344 nummod .5,activation
R1029 T1343 T1344 compound PKA,activation
R1030 T1344 T1346 nsubj activation,leads
R1031 T1345 T1346 advmod then,leads
R1032 T1346 T1346 ROOT leads,leads
R1033 T1347 T1346 prep to,leads
R1034 T1348 T1349 det the,phosphorylation
R1035 T1349 T1347 pobj phosphorylation,to
R1036 T1350 T1349 prep of,phosphorylation
R1037 T1351 T1353 det the,factor
R1038 T1352 T1353 compound transcription,factor
R1039 T1353 T1350 pobj factor,of
R1040 T1354 T1355 amod cAMP-response,element
R1041 T1355 T1365 npadvmod element,into
R1042 T1356 T1357 amod binding,protein
R1043 T1357 T1355 appos protein,element
R1044 T1358 T1359 punct (,CREB
R1045 T1359 T1357 appos CREB,protein
R1046 T1360 T1359 punct ),CREB
R1047 T1361 T1357 punct ",",protein
R1048 T1362 T1357 conj transmission,protein
R1049 T1363 T1362 prep of,transmission
R1050 T1364 T1363 pobj signals,of
R1051 T1365 T1349 prep into,phosphorylation
R1052 T1366 T1367 det the,nucleus
R1053 T1367 T1365 pobj nucleus,into
R1054 T1368 T1346 punct ",",leads
R1055 T1369 T1346 cc and,leads
R1056 T1370 T1372 det the,modulation
R1057 T1371 T1372 amod subsequent,modulation
R1058 T1372 T1346 conj modulation,leads
R1059 T1373 T1372 prep of,modulation
R1060 T1374 T1375 compound gene,transcription
R1061 T1375 T1373 pobj transcription,of
R1062 T1376 T1375 nummod .6,transcription
R1063 T1377 T1381 det This,cascade
R1064 T1378 T1379 advmod apparently,simple
R1065 T1379 T1381 amod simple,cascade
R1066 T1380 T1381 amod linear,cascade
R1067 T1381 T1385 nsubj cascade,explain
R1068 T1382 T1385 aux does,explain
R1069 T1383 T1385 neg not,explain
R1070 T1384 T1385 advmod fully,explain
R1071 T1385 T1385 ROOT explain,explain
R1072 T1386 T1387 det the,mechanism
R1073 T1387 T1385 dobj mechanism,explain
R1074 T1388 T1397 prep by,exerts
R1075 T1389 T1388 pobj which,by
R1076 T1390 T1391 det an,elevation
R1077 T1391 T1397 nsubj elevation,exerts
R1078 T1392 T1391 prep in,elevation
R1079 T1393 T1396 det the,level
R1080 T1394 T1396 amod intracellular,level
R1081 T1395 T1396 compound cAMP,level
R1082 T1396 T1392 pobj level,in
R1083 T1397 T1387 relcl exerts,mechanism
R1084 T1398 T1399 amod wide-ranging,effects
R1085 T1399 T1397 dobj effects,exerts
R1086 T1400 T1399 prep on,effects
R1087 T1401 T1403 amod multiple,functions
R1088 T1402 T1403 amod cellular,functions
R1089 T1403 T1400 pobj functions,on
R1090 T1404 T1385 punct .,explain
R1091 T1405 T1406 expl There,is
R1092 T1406 T1406 ROOT is,is
R1093 T1407 T1409 det a,body
R1094 T1408 T1409 amod growing,body
R1100 T1414 T1416 nsubj cAMP,function
R1101 T1415 T1416 aux may,function
R1102 T1416 T1412 ccomp function,suggesting
R1103 T1417 T1416 prep through,function
R1104 T1418 T1419 preconj both,PKA-dependent
R1105 T1419 T1423 amod PKA-dependent,mechanisms
R1106 T1420 T1419 cc and,PKA-dependent
R1107 T1421 T1419 punct -,PKA-dependent
R1108 T1422 T1423 amod independent,mechanisms
R1109 T1423 T1417 pobj mechanisms,through
R1110 T1424 T1423 appos .6,mechanisms
R1111 T1425 T1427 nummod 8,activation
R1112 T1426 T1427 amod LPS-induced,activation
R1113 T1427 T1439 nsubj activation,been
R1114 T1428 T1427 prep of,activation
R1115 T1429 T1431 det the,factor
R1116 T1430 T1431 compound transcription,factor
R1117 T1431 T1428 pobj factor,of
R1118 T1432 T1433 amod nuclear,factor-κB
R1119 T1433 T1439 nsubj factor-κB,been
R1120 T1434 T1435 punct (,NF-κB
R1121 T1435 T1433 appos NF-κB,factor-κB
R1122 T1436 T1433 punct ),factor-κB
R1123 T1437 T1439 aux has,been
R1124 T1438 T1439 advmod also,been
R1125 T1439 T1406 conj been,is
R1126 T1440 T1441 det the,focus
R1127 T1441 T1439 attr focus,been
R1128 T1442 T1441 prep of,focus
R1129 T1443 T1445 det a,deal
R1130 T1444 T1445 amod great,deal
R1131 T1445 T1442 pobj deal,of
R1132 T1446 T1445 prep of,deal
R1133 T1447 T1446 pobj research,of
R1134 T1448 T1439 punct .,been
R1135 T1449 T1453 nsubjpass It,demonstrated
R1136 T1450 T1453 aux has,demonstrated
R1137 T1451 T1453 auxpass been,demonstrated
R1138 T1452 T1453 advmod clearly,demonstrated
R1139 T1453 T1453 ROOT demonstrated,demonstrated
R1140 T1454 T1461 mark that,inhibit
R1141 T1455 T1461 nsubj agents,inhibit
R1142 T1456 T1457 nsubj that,increase
R1143 T1457 T1455 relcl increase,agents
R1144 T1458 T1459 compound intracellular,cAMP
R1145 T1459 T1457 dobj cAMP,increase
R1146 T1460 T1461 advmod also,inhibit
R1147 T1461 T1453 ccomp inhibit,demonstrated
R1148 T1462 T1465 amod NF-κB-dependent,transcription
R1149 T1463 T1465 amod pro-inflammatory,transcription
R1150 T1464 T1465 compound gene,transcription
R1151 T1465 T1461 dobj transcription,inhibit
R1152 T1466 T1465 punct ",",transcription
R1153 T1467 T1468 advmod particularly,of
R1154 T1468 T1465 prep of,transcription
R1155 T1469 T1471 det the,gene
R1156 T1470 T1471 compound TNF-α,gene
R1157 T1471 T1468 pobj gene,of
R1158 T1472 T1473 nummod .9,Controversy
R1159 T1473 T1474 nsubj Controversy,exists
R1160 T1474 T1465 relcl exists,transcription
R1161 T1475 T1474 prep regarding,exists
R1162 T1476 T1478 det the,mechanism
R1163 T1477 T1478 amod exact,mechanism
R1164 T1478 T1475 pobj mechanism,regarding
R1165 T1479 T1478 punct (,mechanism
R1166 T1480 T1478 appos s,mechanism
R1167 T1481 T1478 punct ),mechanism
R1168 T1482 T1486 prep by,down-regulates
R1169 T1483 T1482 pobj which,by
R1170 T1484 T1486 nmod PDE,down-regulates
R1171 T1485 T1486 compound inhibition,down-regulates
R1172 T1486 T1474 conj down-regulates,exists
R1173 T1487 T1488 amod TNF-α,production
R1174 T1488 T1486 dobj production,down-regulates
R1175 T1489 T1453 punct .,demonstrated
R1176 T1490 T1491 nsubj Possibilities,include
R1177 T1491 T1491 ROOT include,include
R1178 T1492 T1491 punct ",",include
R1179 T1493 T1491 cc but,include
R1180 T1494 T1496 auxpass are,limited
R1181 T1495 T1496 neg not,limited
R1182 T1496 T1491 conj limited,include
R1183 T1497 T1496 prep to,limited
R1184 T1498 T1497 punct ",",to
R1185 T1499 T1497 pobj inhibition,to
R1186 T1500 T1499 prep of,inhibition
R1187 T1501 T1502 compound NF-κB,DNA
R1188 T1502 T1500 pobj DNA,of
R1189 T1503 T1504 amod binding,activity
R1190 T1504 T1499 conj activity,inhibition
R1191 T1505 T1499 punct ",",inhibition
R1192 T1506 T1499 appos downregulation,inhibition
R1193 T1507 T1506 prep of,downregulation
R1194 T1508 T1510 amod NF-κB,activity
R1195 T1509 T1510 amod transcriptional,activity
R1196 T1510 T1507 pobj activity,of
R1197 T1511 T1512 punct ",",increased
R1198 T1512 T1514 amod increased,activation
R1199 T1513 T1514 compound CREB,activation
R1200 T1514 T1496 dobj activation,limited
R1201 T1515 T1514 punct ",",activation
R1202 T1516 T1514 cc and,activation
R1203 T1517 T1514 conj competition,activation
R1204 T1518 T1514 prep between,activation
R1205 T1519 T1518 pobj NF-κB,between
R1206 T1520 T1519 cc and,NF-κB
R1207 T1521 T1519 conj CREB,NF-κB
R1208 T1522 T1514 prep for,activation
R1209 T1523 T1524 amod common,co-activators
R1210 T1524 T1522 pobj co-activators,for
R1211 T1525 T1526 amod such,as
R1212 T1526 T1524 prep as,co-activators
R1213 T1527 T1526 pobj CREB,as
R1214 T1528 T1529 amod binding,protein
R1215 T1529 T1527 appos protein,CREB
R1216 T1530 T1531 punct (,CBP
R1217 T1531 T1529 appos CBP,protein
R1218 T1532 T1527 punct ),CREB
R1219 T1533 T1491 punct .,include
R1220 T1534 T1535 nsubj It,is
R1221 T1535 T1538 auxpass is,known
R1222 T1536 T1535 advmod also,is
R1223 T1537 T1538 neg not,known
R1224 T1538 T1538 ROOT known,known
R1225 T1539 T1542 mark whether,rely
R1226 T1540 T1541 det these,processes
R1227 T1541 T1542 nsubj processes,rely
R1228 T1542 T1538 ccomp rely,known
R1229 T1543 T1544 advmod solely,upon
R1230 T1544 T1542 prep upon,rely
R1231 T1545 T1546 det the,activation
R1232 T1546 T1544 pobj activation,upon
R1233 T1547 T1546 prep of,activation
R1234 T1548 T1547 pobj PKA,of
R1235 T1549 T1538 punct .,known
R1236 T1550 T1558 advmod Therefore,is
R1237 T1551 T1558 punct ",",is
R1238 T1552 T1553 det the,objective
R1239 T1553 T1558 nsubj objective,is
R1240 T1554 T1553 prep of,objective
R1241 T1555 T1557 det the,study
R1242 T1556 T1557 amod present,study
R1243 T1557 T1554 pobj study,of
R1244 T1558 T1558 ROOT is,is
R1245 T1559 T1560 aux to,determine
R1246 T1560 T1558 xcomp determine,is
R1247 T1561 T1562 det the,effects
R1248 T1562 T1560 dobj effects,determine
R1249 T1563 T1562 prep of,effects
R1250 T1564 T1566 amod nonspecific,inhibition
R1251 T1565 T1566 compound PDE,inhibition
R1252 T1566 T1563 pobj inhibition,of
R1253 T1567 T1562 prep with,effects
R1254 T1568 T1570 meta 1,[
R1255 T1569 T1570 punct -,[
R1256 T1570 T1572 compound [,]
R1257 T1571 T1572 compound 5-oxohexyl,]
R1258 T1572 T1567 pobj ],with
R1259 T1573 T1575 nummod "-3,7",dimethylxanthine
R1260 T1574 T1575 punct -,dimethylxanthine
R1261 T1575 T1572 appos dimethylxanthine,]
R1262 T1576 T1577 punct (,Pentoxifylline
R1263 T1577 T1575 dep Pentoxifylline,dimethylxanthine
R1264 T1578 T1577 punct ;,Pentoxifylline
R1265 T1579 T1577 appos PTX,Pentoxifylline
R1266 T1580 T1577 punct ),Pentoxifylline
R1267 T1581 T1577 prep on,Pentoxifylline
R1268 T1582 T1581 pobj NF-κB,on
R1269 T1583 T1582 cc and,NF-κB
R1270 T1584 T1585 compound CREB,activation
R1271 T1585 T1582 conj activation,NF-κB
R1272 T1586 T1585 prep in,activation
R1273 T1587 T1586 pobj vitro,in
R1274 T1588 T1585 prep in,activation
R1275 T1589 T1591 amod human,cells
R1276 T1590 T1591 compound mononuclear,cells
R1277 T1591 T1588 pobj cells,in
R1278 T1592 T1558 punct .,is
R1279 T1593 T1602 prep With,investigated
R1280 T1594 T1595 det the,use
R1281 T1595 T1593 pobj use,With
R1282 T1596 T1595 prep of,use
R1283 T1597 T1598 amod specific,inhibitors
R1284 T1598 T1596 pobj inhibitors,of
R1285 T1599 T1602 punct ",",investigated
R1286 T1600 T1602 nsubj we,investigated
R1287 T1601 T1602 advmod also,investigated
R1288 T1602 T1602 ROOT investigated,investigated
R1289 T1603 T1604 det the,role
R1290 T1604 T1602 dobj role,investigated
R1291 T1605 T1604 prep of,role
R1292 T1606 T1605 pobj PKA,of
R1293 T1607 T1604 prep in,role
R1294 T1608 T1610 amod LPS-induced,production
R1295 T1609 T1610 compound TNF-α,production
R1296 T1610 T1607 pobj production,in
R1297 T1611 T1602 punct .,investigated
R1891 T2464 T2465 det this,study
R1892 T2465 T2467 nsubjpass study,approved
R1893 T2466 T2467 auxpass was,approved
R1894 T2467 T2467 ROOT approved,approved
R1895 T2468 T2467 agent by,approved
R1896 T2469 T2473 det the,Program
R1897 T2470 T2472 compound Human,Protections
R1898 T2471 T2472 compound Research,Protections
R1899 T2472 T2473 compound Protections,Program
R1900 T2473 T2468 pobj Program,by
R1901 T2474 T2473 cc and,Program
R1902 T2475 T2478 det the,Board
R1903 T2476 T2478 compound Institutional,Board
R1904 T2477 T2478 compound Review,Board
R1905 T2478 T2473 conj Board,Program
R1906 T2479 T2467 punct .,approved
R1907 T2480 T2481 amod Written,consent
R1908 T2481 T2488 nsubjpass consent,obtained
R1909 T2482 T2483 aux to,participate
R1910 T2483 T2481 relcl participate,consent
R1911 T2484 T2483 prep in,participate
R1912 T2485 T2486 det the,study
R1913 T2486 T2484 pobj study,in
R1914 T2487 T2488 auxpass was,obtained
R1915 T2488 T2488 ROOT obtained,obtained
R1916 T2489 T2488 prep from,obtained
R1917 T2490 T2491 det all,volunteers
R1918 T2491 T2489 pobj volunteers,from
R1919 T2492 T2488 advmod prior,obtained
R1920 T2493 T2492 prep to,prior
R1921 T2494 T2493 pobj blood,to
R1922 T2495 T2496 amod "donation. Heparinized",Vacutainers
R1923 T2496 T2493 pobj Vacutainers,to
R1924 T2497 T2498 auxpass were,purchased
R1925 T2498 T2488 conj purchased,obtained
R1926 T2499 T2498 prep from,purchased
R1927 T2500 T2501 compound Becton,Dickinson
R1928 T2501 T2499 pobj Dickinson,from
R1929 T2502 T2501 punct (,Dickinson
R1930 T2503 T2504 compound San,Jose
R1931 T2504 T2501 appos Jose,Dickinson
R1932 T2505 T2504 punct ",",Jose
R1933 T2506 T2501 conj CA,Dickinson
R1934 T2507 T2488 punct ),obtained
R1935 T2508 T2488 punct .,obtained
R100 T202 T200 pobj sepsis,in
R101 T203 T202 cc and,sepsis
R102 T204 T202 conj inflammation,sepsis
R339 T441 T443 det a,tool
R340 T442 T443 amod useful,tool
R341 T443 T440 pobj tool,as
R342 T444 T443 prep in,tool
R343 T445 T446 det the,attenuation
R344 T446 T444 pobj attenuation,in
R345 T447 T446 prep of,attenuation
R346 T448 T449 amod LPS-induced,inflammation
R347 T449 T447 pobj inflammation,of
R925 T1239 T1223 conj is,shown
R926 T1240 T1243 det a,cytokine
R927 T1241 T1243 amod potent,cytokine
R928 T1242 T1243 amod pro-inflammatory,cytokine
R929 T1243 T1239 attr cytokine,is
R930 T1244 T1243 acl involved,cytokine
R931 T1245 T1244 prep in,involved
R932 T1246 T1248 det a,spectrum
R933 T1247 T1248 amod wide,spectrum
R934 T1248 T1245 pobj spectrum,in
R935 T1249 T1248 prep of,spectrum
R936 T1250 T1251 amod cellular,responses
R937 T1251 T1249 pobj responses,of
R1095 T1409 T1406 attr body,is
R1096 T1410 T1409 prep of,body
R1097 T1411 T1410 pobj evidence,of
R1098 T1412 T1411 acl suggesting,evidence
R1099 T1413 T1416 mark that,function
R60 T162 T159 pobj inhibition,of
R61 T163 T162 prep on,inhibition
R62 T164 T165 compound transcription,factor
R63 T165 T166 compound factor,activation
R64 T166 T163 pobj activation,on
R65 T167 T166 cc and,activation
R66 T168 T169 compound tumor,necrosis
R67 T169 T170 compound necrosis,factor-alpha
R68 T170 T166 conj factor-alpha,activation
R69 T171 T172 punct (,TNF-α
R70 T172 T170 appos TNF-α,factor-alpha
R71 T173 T170 punct ),factor-alpha
R72 T174 T166 conj production,activation
R73 T175 T174 prep in,production
R74 T176 T175 pobj lipopolysaccharide,in
R75 T177 T178 punct (,LPS
R76 T178 T176 appos LPS,lipopolysaccharide
R77 T179 T176 punct ),lipopolysaccharide

UBERON-AE

Id Subject Object Predicate Lexical cue
T1125 2297-2310 http://purl.obolibrary.org/obo/UBERON_0002405 denotes immune system
T2438 4959-4964 http://purl.obolibrary.org/obo/UBERON_0000178 denotes blood

GO-BP

Id Subject Object Predicate Lexical cue
T826 151-168 http://purl.obolibrary.org/obo/GO_0032680 denotes TNF-α) production
T827 251-270 http://purl.obolibrary.org/obo/GO_0032680 denotes production of TNF-α
T828 418-434 http://purl.obolibrary.org/obo/GO_0032680 denotes TNF-α production
T834 151-168 http://purl.obolibrary.org/obo/GO_0032640 denotes TNF-α) production
T835 251-270 http://purl.obolibrary.org/obo/GO_0032640 denotes production of TNF-α
T836 251-268 http://purl.obolibrary.org/obo/GO_0032640 denotes production of TNF
T838 54-71 http://purl.obolibrary.org/obo/GO_0008081 denotes phosphodiesterase
T839 382-399 http://purl.obolibrary.org/obo/GO_0008081 denotes phosphodiesterase
T840 618-635 http://purl.obolibrary.org/obo/GO_0008081 denotes phosphodiesterase
T841 1500-1517 http://purl.obolibrary.org/obo/GO_0008081 denotes phosphodiesterase
T842 1753-1770 http://purl.obolibrary.org/obo/GO_0008081 denotes phosphodiesterase
T843 72-106 http://purl.obolibrary.org/obo/GO_1901484 denotes inhibition on transcription factor
T844 72-106 http://purl.obolibrary.org/obo/GO_0043433 denotes inhibition on transcription factor
T845 72-106 http://purl.obolibrary.org/obo/GO_0032792 denotes inhibition on transcription factor
T846 86-99 http://purl.obolibrary.org/obo/GO_0006351 denotes transcription
T847 1634-1649 http://purl.obolibrary.org/obo/GO_0006351 denotes transcriptional
T848 86-117 http://purl.obolibrary.org/obo/GO_0051091 denotes transcription factor activation
T849 86-117 http://purl.obolibrary.org/obo/GO_0032793 denotes transcription factor activation
T850 1615-1633 http://purl.obolibrary.org/obo/GO_0032793 denotes activation of CREB
T851 86-117 http://purl.obolibrary.org/obo/GO_1901485 denotes transcription factor activation
T852 128-136 http://purl.obolibrary.org/obo/GO_0001906 denotes necrosis
T853 128-136 http://purl.obolibrary.org/obo/GO_0008219 denotes necrosis
T854 128-136 http://purl.obolibrary.org/obo/GO_0019835 denotes necrosis
T855 128-136 http://purl.obolibrary.org/obo/GO_0070265 denotes necrosis
T856 345-357 http://purl.obolibrary.org/obo/GO_0006954 denotes inflammation
T857 1911-1923 http://purl.obolibrary.org/obo/GO_0006954 denotes inflammation
T858 618-645 http://purl.obolibrary.org/obo/GO_0051344 denotes phosphodiesterase inhibitor
T859 744-757 http://purl.obolibrary.org/obo/GO_0051591 denotes cAMP-response
T860 1133-1148 http://purl.obolibrary.org/obo/GO_0016310 denotes phosphorylation
T861 1162-1177 http://purl.obolibrary.org/obo/GO_0016310 denotes phosphorylation
T862 1257-1272 http://purl.obolibrary.org/obo/GO_0016310 denotes phosphorylation
T863 1601-1625 http://purl.obolibrary.org/obo/GO_0051092 denotes NF-κB and the activation
T2109 2023-2038 http://purl.obolibrary.org/obo/GO_0016310 denotes phosphorylation
T2110 3137-3152 http://purl.obolibrary.org/obo/GO_0016310 denotes phosphorylation
T2111 2023-2053 http://purl.obolibrary.org/obo/GO_0042327 denotes phosphorylation and activation
T2112 2071-2100 http://purl.obolibrary.org/obo/GO_0035556 denotes intracellular protein kinases
T2113 2105-2118 http://purl.obolibrary.org/obo/GO_0006351 denotes transcription
T2114 2201-2214 http://purl.obolibrary.org/obo/GO_0006351 denotes transcription
T2115 2327-2340 http://purl.obolibrary.org/obo/GO_0006351 denotes transcription
T2116 3160-3173 http://purl.obolibrary.org/obo/GO_0006351 denotes transcription
T2117 3307-3320 http://purl.obolibrary.org/obo/GO_0006351 denotes transcription
T2118 3671-3684 http://purl.obolibrary.org/obo/GO_0006351 denotes transcription
T2119 3900-3913 http://purl.obolibrary.org/obo/GO_0006351 denotes transcription
T2120 4170-4185 http://purl.obolibrary.org/obo/GO_0006351 denotes transcriptional
T2121 2128-2159 http://purl.obolibrary.org/obo/GO_0051091 denotes Transcription factor activation
T2122 2327-2358 http://purl.obolibrary.org/obo/GO_0051091 denotes transcription factor activation
T2123 3653-3691 http://purl.obolibrary.org/obo/GO_0051091 denotes activation of the transcription factor
T2124 2128-2159 http://purl.obolibrary.org/obo/GO_0032793 denotes Transcription factor activation
T2125 2327-2358 http://purl.obolibrary.org/obo/GO_0032793 denotes transcription factor activation
T2126 3653-3691 http://purl.obolibrary.org/obo/GO_0032793 denotes activation of the transcription factor
T2127 4206-4221 http://purl.obolibrary.org/obo/GO_0032793 denotes CREB activation
T2128 4588-4603 http://purl.obolibrary.org/obo/GO_0032793 denotes CREB activation
T2129 2128-2159 http://purl.obolibrary.org/obo/GO_1901485 denotes Transcription factor activation
T2130 2327-2358 http://purl.obolibrary.org/obo/GO_1901485 denotes transcription factor activation
T2131 3653-3691 http://purl.obolibrary.org/obo/GO_1901485 denotes activation of the transcription factor
T2132 2219-2236 http://purl.obolibrary.org/obo/GO_0006412 denotes protein synthesis
T2133 2227-2236 http://purl.obolibrary.org/obo/GO_0009058 denotes synthesis
T2134 2558-2567 http://purl.obolibrary.org/obo/GO_0009058 denotes synthesis
T2135 2405-2413 http://purl.obolibrary.org/obo/GO_0001906 denotes necrosis
T2136 2405-2413 http://purl.obolibrary.org/obo/GO_0008219 denotes necrosis
T2137 2405-2413 http://purl.obolibrary.org/obo/GO_0019835 denotes necrosis
T2138 2405-2413 http://purl.obolibrary.org/obo/GO_0070265 denotes necrosis
T2139 2424-2441 http://purl.obolibrary.org/obo/GO_0032640 denotes TNF-α) production
T2140 2810-2826 http://purl.obolibrary.org/obo/GO_0032640 denotes TNF-α production
T2141 4039-4055 http://purl.obolibrary.org/obo/GO_0032640 denotes TNF-α production
T2142 4730-4746 http://purl.obolibrary.org/obo/GO_0032640 denotes TNF-α production
T2143 2424-2441 http://purl.obolibrary.org/obo/GO_0032680 denotes TNF-α) production
T2144 2810-2826 http://purl.obolibrary.org/obo/GO_0032680 denotes TNF-α production
T2145 4039-4055 http://purl.obolibrary.org/obo/GO_0032680 denotes TNF-α production
T2146 4730-4746 http://purl.obolibrary.org/obo/GO_0032680 denotes TNF-α production
T2147 2519-2527 http://purl.obolibrary.org/obo/GO_0007349 denotes cellular
T2148 3492-3500 http://purl.obolibrary.org/obo/GO_0007349 denotes cellular
T2149 2613-2630 http://purl.obolibrary.org/obo/GO_0008081 denotes phosphodiesterase
T2150 2632-2635 http://purl.obolibrary.org/obo/GO_0004114 denotes PDE
T2151 2747-2750 http://purl.obolibrary.org/obo/GO_0004114 denotes PDE
T2152 2927-2930 http://purl.obolibrary.org/obo/GO_0004114 denotes PDE
T2153 4009-4012 http://purl.obolibrary.org/obo/GO_0004114 denotes PDE
T2154 4497-4500 http://purl.obolibrary.org/obo/GO_0004114 denotes PDE
T2155 2714-2723 http://purl.obolibrary.org/obo/GO_0023052 denotes signaling
T2156 3243-3250 http://purl.obolibrary.org/obo/GO_0023052 denotes signals
T2157 2792-2815 http://purl.obolibrary.org/obo/GO_1904468 denotes downregulation of TNF-α
T2158 3065-3093 http://purl.obolibrary.org/obo/GO_0034199 denotes activation of Protein kinase
T2159 3065-3093 http://purl.obolibrary.org/obo/GO_0032147 denotes activation of Protein kinase
T2160 3065-3093 http://purl.obolibrary.org/obo/GO_0030295 denotes activation of Protein kinase
T2161 3097-3100 http://purl.obolibrary.org/obo/GO_0004691 denotes PKA
T2162 3104-3107 http://purl.obolibrary.org/obo/GO_0004691 denotes PKA
T2163 3595-3598 http://purl.obolibrary.org/obo/GO_0004691 denotes PKA
T2164 4403-4406 http://purl.obolibrary.org/obo/GO_0004691 denotes PKA
T2165 4711-4714 http://purl.obolibrary.org/obo/GO_0004691 denotes PKA
T2166 3181-3194 http://purl.obolibrary.org/obo/GO_0051591 denotes cAMP-response
T2167 3854-3867 http://purl.obolibrary.org/obo/GO_0032088 denotes inhibit NF-κB
T2168 3854-3867 http://purl.obolibrary.org/obo/GO_0007252 denotes inhibit NF-κB
T3127 5047-5049 http://purl.obolibrary.org/obo/GO_0033968 denotes CA

GO-MF

Id Subject Object Predicate Lexical cue
T865 54-71 http://purl.obolibrary.org/obo/GO_0008081 denotes phosphodiesterase
T866 382-399 http://purl.obolibrary.org/obo/GO_0008081 denotes phosphodiesterase
T867 618-635 http://purl.obolibrary.org/obo/GO_0008081 denotes phosphodiesterase
T868 1500-1517 http://purl.obolibrary.org/obo/GO_0008081 denotes phosphodiesterase
T869 1753-1770 http://purl.obolibrary.org/obo/GO_0008081 denotes phosphodiesterase
T870 766-773 http://purl.obolibrary.org/obo/GO_0005488 denotes binding
T871 808-815 http://purl.obolibrary.org/obo/GO_0005488 denotes binding
T872 1191-1198 http://purl.obolibrary.org/obo/GO_0005488 denotes binding
T873 1281-1288 http://purl.obolibrary.org/obo/GO_0005488 denotes binding
T874 1654-1661 http://purl.obolibrary.org/obo/GO_0005488 denotes binding
T875 766-781 http://purl.obolibrary.org/obo/GO_0005515 denotes binding protein
T876 804-815 http://purl.obolibrary.org/obo/GO_0003677 denotes DNA binding
T877 1187-1198 http://purl.obolibrary.org/obo/GO_0003677 denotes DNA binding
T878 1277-1288 http://purl.obolibrary.org/obo/GO_0003677 denotes DNA binding
T879 1650-1661 http://purl.obolibrary.org/obo/GO_0003677 denotes DNA binding
T880 808-824 http://purl.obolibrary.org/obo/GO_0051059 denotes binding of NF-κB
T2192 2327-2358 http://purl.obolibrary.org/obo/GO_0033613 denotes transcription factor activation
T2193 3653-3691 http://purl.obolibrary.org/obo/GO_0033613 denotes activation of the transcription factor
T2194 2613-2630 http://purl.obolibrary.org/obo/GO_0008081 denotes phosphodiesterase
T2195 2632-2635 http://purl.obolibrary.org/obo/GO_0004114 denotes PDE
T2196 2747-2750 http://purl.obolibrary.org/obo/GO_0004114 denotes PDE
T2197 2927-2930 http://purl.obolibrary.org/obo/GO_0004114 denotes PDE
T2198 4009-4012 http://purl.obolibrary.org/obo/GO_0004114 denotes PDE
T2199 4497-4500 http://purl.obolibrary.org/obo/GO_0004114 denotes PDE
T2200 3065-3093 http://purl.obolibrary.org/obo/GO_0030295 denotes activation of Protein kinase
T2201 3097-3100 http://purl.obolibrary.org/obo/GO_0004691 denotes PKA
T2202 3104-3107 http://purl.obolibrary.org/obo/GO_0004691 denotes PKA
T2203 3595-3598 http://purl.obolibrary.org/obo/GO_0004691 denotes PKA
T2204 4403-4406 http://purl.obolibrary.org/obo/GO_0004691 denotes PKA
T2205 4711-4714 http://purl.obolibrary.org/obo/GO_0004691 denotes PKA
T2206 3203-3210 http://purl.obolibrary.org/obo/GO_0005488 denotes binding
T2207 4128-4135 http://purl.obolibrary.org/obo/GO_0005488 denotes binding
T2208 4300-4307 http://purl.obolibrary.org/obo/GO_0005488 denotes binding
T2209 3203-3218 http://purl.obolibrary.org/obo/GO_0005515 denotes binding protein
T2210 4300-4315 http://purl.obolibrary.org/obo/GO_0005515 denotes binding protein
T2211 4124-4135 http://purl.obolibrary.org/obo/GO_0003677 denotes DNA binding
T2212 4295-4307 http://purl.obolibrary.org/obo/GO_0008140 denotes CREB binding
T2213 4317-4320 http://purl.obolibrary.org/obo/GO_0008140 denotes CBP
T3144 5047-5049 http://purl.obolibrary.org/obo/GO_0033968 denotes CA

GO-CC

Id Subject Object Predicate Lexical cue
T881 226-231 http://purl.obolibrary.org/obo/GO_0005623 denotes cells
T882 502-507 http://purl.obolibrary.org/obo/GO_0005623 denotes cells
T883 950-955 http://purl.obolibrary.org/obo/GO_0005623 denotes cells
T2214 1954-1962 http://purl.obolibrary.org/obo/GO_0016020 denotes membrane
T2215 2066-2070 http://purl.obolibrary.org/obo/GO_0018995 denotes host
T2216 2292-2296 http://purl.obolibrary.org/obo/GO_0018995 denotes host
T2217 2066-2084 http://purl.obolibrary.org/obo/GO_0043656 denotes host intracellular
T2218 2071-2084 http://purl.obolibrary.org/obo/GO_0005622 denotes intracellular
T2219 2957-2970 http://purl.obolibrary.org/obo/GO_0005622 denotes intracellular
T2220 3427-3440 http://purl.obolibrary.org/obo/GO_0005622 denotes intracellular
T2221 3830-3843 http://purl.obolibrary.org/obo/GO_0005622 denotes intracellular
T2222 2596-2601 http://purl.obolibrary.org/obo/GO_0005623 denotes cells
T2223 2877-2882 http://purl.obolibrary.org/obo/GO_0005623 denotes cells
T2224 4634-4639 http://purl.obolibrary.org/obo/GO_0005623 denotes cells
T2225 3097-3100 http://purl.obolibrary.org/obo/GO_0005952 denotes PKA
T2226 3104-3107 http://purl.obolibrary.org/obo/GO_0005952 denotes PKA
T2227 3595-3598 http://purl.obolibrary.org/obo/GO_0005952 denotes PKA
T2228 4403-4406 http://purl.obolibrary.org/obo/GO_0005952 denotes PKA
T2229 4711-4714 http://purl.obolibrary.org/obo/GO_0005952 denotes PKA
T2230 3260-3267 http://purl.obolibrary.org/obo/GO_0005634 denotes nucleus
T2231 3671-3699 http://purl.obolibrary.org/obo/GO_0044798 denotes transcription factor nuclear

sentences

Id Subject Object Predicate Lexical cue
T114 234-246 Sentence denotes INTRODUCTION
T115 247-358 Sentence denotes The production of TNF-α following LPS stimulation is one of the key steps in bacterial sepsis and inflammation.
T116 359-474 Sentence denotes The mechanism by which phosphodiesterase inhibition alters TNF-α production in the presence of LPS remains unclear.
T117 476-483 Sentence denotes METHODS
T118 484-646 Sentence denotes Human mononuclear cells were stimulated with LPS (1 μg/mL), in the presence and absence of Pentoxifylline (PTX; 20 mM), a nonspecific phosphodiesterase inhibitor.
T119 647-803 Sentence denotes Western blotting of phosphorylated cytoplasmic I-κBα, nuclear factor-κB p65 (NF-κB), and nuclear cAMP-response element binding protein (CREB) was performed.
T120 804-887 Sentence denotes DNA binding of NF-κB and CREB was verified by electrophoretic mobility shift assay.
T121 888-1060 Sentence denotes TNF-α levels were determined in the supernatant of stimulated cells in the presence and absence Protein kinase A inhibition by an enzyme-linked immunosorbent assay (ELISA).
T122 1062-1069 Sentence denotes RESULTS
T123 1070-1217 Sentence denotes PTX was demonstrated to significantly reduce cytoplasmic I-κBα phosphorylation, nuclear p65 phosphorylation, and the DNA binding activity of NF-κB.
T124 1218-1306 Sentence denotes In contrast, PTX markedly enhanced the phosphorylation and DNA binding activity of CREB.
T125 1307-1441 Sentence denotes Cells concomitantly treated with PTX and LPS secreted similar levels of TNF-α in the presence and absence Protein kinase A inhibition.
T126 1443-1453 Sentence denotes DISCUSSION
T127 1454-1727 Sentence denotes The increased level of cAMP that results from phosphodiesterase inhibition affects cytoplasmic and nuclear events, resulting in the attenuation of NF-κB and the activation of CREB transcriptional DNA binding through pathways that are partially Protein kinase A-independent.
T128 1729-1739 Sentence denotes CONCLUSION
T129 1740-1924 Sentence denotes PTX-mediated phosphodiesterase inhibition occurs partially through a Protein kinase A-independent pathway and may serve as a useful tool in the attenuation of LPS-induced inflammation.
T1149 1940-2127 Sentence denotes The bacterial membrane component lipopolysaccharide (LPS) is capable of initiating phosphorylation and activation of multiple host intracellular protein kinases and transcription factors.
T1150 2128-2314 Sentence denotes Transcription factor activation, which results in the modulation of gene transcription and protein synthesis, is a critical element in the defense mechanism of the host immune system.1,2
T1151 2315-2538 Sentence denotes LPS-induced transcription factor activation has been shown to be a key regulator of tumor necrosis factor-α (TNF-α) production.3 TNF-α is a potent pro-inflammatory cytokine involved in a wide spectrum of cellular responses.
T1152 2539-2883 Sentence denotes Furthermore, TNF-α synthesis can be attenuated in immune cells exposed to phosphodiesterase (PDE) inhibition after challenge by a variety of pro-inflammatory stimulants.4 The signaling mechanisms affected by PDE inhibition, which ultimately lead to the downregulation of TNF-α production, have not been well characterized in inflammatory cells.
T1153 2884-3511 Sentence denotes Classically, it has been demonstrated that PDE inhibition results in the intracellular accumulation of the second messenger cyclic adenosine-3,5-monophosphate (cAMP) and subsequent activation of Protein kinase A (PKA).5 PKA activation then leads to the phosphorylation of the transcription factor cAMP-response element binding protein (CREB), transmission of signals into the nucleus, and the subsequent modulation of gene transcription.6 This apparently simple linear cascade does not fully explain the mechanism by which an elevation in the intracellular cAMP level exerts wide-ranging effects on multiple cellular functions.
T1154 3512-3640 Sentence denotes There is a growing body of evidence suggesting that cAMP may function through both PKA-dependent and -independent mechanisms.6–8
T1155 3641-3770 Sentence denotes LPS-induced activation of the transcription factor nuclear factor-κB (NF-κB) has also been the focus of a great deal of research.
T1156 3771-3947 Sentence denotes It has been clearly demonstrated that agents that increase intracellular cAMP also inhibit NF-κB-dependent pro-inflammatory gene transcription, particularly of the TNF-α gene.9
T1157 3948-4056 Sentence denotes Controversy exists regarding the exact mechanism(s) by which PDE inhibition down-regulates TNF-α production.
T1158 4057-4322 Sentence denotes Possibilities include, but are not limited to, inhibition of NF-κB DNA binding activity, downregulation of NF-κB transcriptional activity, increased CREB activation, and competition between NF-κB and CREB for common co-activators such as CREB binding protein (CBP).
T1159 4323-4407 Sentence denotes It is also not known whether these processes rely solely upon the activation of PKA.
T1160 4408-4640 Sentence denotes Therefore, the objective of the present study is to determine the effects of nonspecific PDE inhibition with 1-[5-oxohexyl]-3,7-dimethylxanthine (Pentoxifylline; PTX) on NF-κB and CREB activation in vitro in human mononuclear cells.
T1161 4641-4747 Sentence denotes With the use of specific inhibitors, we also investigated the role of PKA in LPS-induced TNF-α production.
T2453 0-5051 Sentence denotes this study was to determine the effect of nonspecific phosphodiesterase inhibition on transcription factor activation and tumor necrosis factor-alpha (TNF-α) production in lipopolysaccharide (LPS)-stimulated human mononuclear cells. INTRODUCTION The production of TNF-α following LPS stimulation is one of the key steps in bacterial sepsis and inflammation. The mechanism by which phosphodiesterase inhibition alters TNF-α production in the presence of LPS remains unclear. METHODS Human mononuclear cells were stimulated with LPS (1 μg/mL), in the presence and absence of Pentoxifylline (PTX; 20 mM), a nonspecific phosphodiesterase inhibitor. Western blotting of phosphorylated cytoplasmic I-κBα, nuclear factor-κB p65 (NF-κB), and nuclear cAMP-response element binding protein (CREB) was performed. DNA binding of NF-κB and CREB was verified by electrophoretic mobility shift assay. TNF-α levels were determined in the supernatant of stimulated cells in the presence and absence Protein kinase A inhibition by an enzyme-linked immunosorbent assay (ELISA). RESULTS PTX was demonstrated to significantly reduce cytoplasmic I-κBα phosphorylation, nuclear p65 phosphorylation, and the DNA binding activity of NF-κB. In contrast, PTX markedly enhanced the phosphorylation and DNA binding activity of CREB. Cells concomitantly treated with PTX and LPS secreted similar levels of TNF-α in the presence and absence Protein kinase A inhibition. DISCUSSION The increased level of cAMP that results from phosphodiesterase inhibition affects cytoplasmic and nuclear events, resulting in the attenuation of NF-κB and the activation of CREB transcriptional DNA binding through pathways that are partially Protein kinase A-independent. CONCLUSION PTX-mediated phosphodiesterase inhibition occurs partially through a Protein kinase A-independent pathway and may serve as a useful tool in the attenuation of LPS-induced inflammation. INTRODUCTION The bacterial membrane component lipopolysaccharide (LPS) is capable of initiating phosphorylation and activation of multiple host intracellular protein kinases and transcription factors. Transcription factor activation, which results in the modulation of gene transcription and protein synthesis, is a critical element in the defense mechanism of the host immune system.1,2 LPS-induced transcription factor activation has been shown to be a key regulator of tumor necrosis factor-α (TNF-α) production.3 TNF-α is a potent pro-inflammatory cytokine involved in a wide spectrum of cellular responses. Furthermore, TNF-α synthesis can be attenuated in immune cells exposed to phosphodiesterase (PDE) inhibition after challenge by a variety of pro-inflammatory stimulants.4 The signaling mechanisms affected by PDE inhibition, which ultimately lead to the downregulation of TNF-α production, have not been well characterized in inflammatory cells. Classically, it has been demonstrated that PDE inhibition results in the intracellular accumulation of the second messenger cyclic adenosine-3,5-monophosphate (cAMP) and subsequent activation of Protein kinase A (PKA).5 PKA activation then leads to the phosphorylation of the transcription factor cAMP-response element binding protein (CREB), transmission of signals into the nucleus, and the subsequent modulation of gene transcription.6 This apparently simple linear cascade does not fully explain the mechanism by which an elevation in the intracellular cAMP level exerts wide-ranging effects on multiple cellular functions. There is a growing body of evidence suggesting that cAMP may function through both PKA-dependent and -independent mechanisms.6–8 LPS-induced activation of the transcription factor nuclear factor-κB (NF-κB) has also been the focus of a great deal of research. It has been clearly demonstrated that agents that increase intracellular cAMP also inhibit NF-κB-dependent pro-inflammatory gene transcription, particularly of the TNF-α gene.9 Controversy exists regarding the exact mechanism(s) by which PDE inhibition down-regulates TNF-α production. Possibilities include, but are not limited to, inhibition of NF-κB DNA binding activity, downregulation of NF-κB transcriptional activity, increased CREB activation, and competition between NF-κB and CREB for common co-activators such as CREB binding protein (CBP). It is also not known whether these processes rely solely upon the activation of PKA. Therefore, the objective of the present study is to determine the effects of nonspecific PDE inhibition with 1-[5-oxohexyl]-3,7-dimethylxanthine (Pentoxifylline; PTX) on NF-κB and CREB activation in vitro in human mononuclear cells. With the use of specific inhibitors, we also investigated the role of PKA in LPS-induced TNF-α production. MATERIALS AND METHODS This study was approved by the Human Research Protections Program and the Institutional Review Board. Written consent to participate in the study was obtained from all volunteers prior to blood donation. Heparinized Vacutainers were purchased from Becton Dickinson (San Jose, CA).
T6 234-246 Sentence denotes INTRODUCTION
T7 247-358 Sentence denotes The production of TNF-α following LPS stimulation is one of the key steps in bacterial sepsis and inflammation.
T8 359-474 Sentence denotes The mechanism by which phosphodiesterase inhibition alters TNF-α production in the presence of LPS remains unclear.
T9 476-483 Sentence denotes METHODS
T10 484-646 Sentence denotes Human mononuclear cells were stimulated with LPS (1 μg/mL), in the presence and absence of Pentoxifylline (PTX; 20 mM), a nonspecific phosphodiesterase inhibitor.
T11 647-803 Sentence denotes Western blotting of phosphorylated cytoplasmic I-κBα, nuclear factor-κB p65 (NF-κB), and nuclear cAMP-response element binding protein (CREB) was performed.
T12 804-887 Sentence denotes DNA binding of NF-κB and CREB was verified by electrophoretic mobility shift assay.
T13 888-1060 Sentence denotes TNF-α levels were determined in the supernatant of stimulated cells in the presence and absence Protein kinase A inhibition by an enzyme-linked immunosorbent assay (ELISA).
T14 1062-1069 Sentence denotes RESULTS
T15 1070-1217 Sentence denotes PTX was demonstrated to significantly reduce cytoplasmic I-κBα phosphorylation, nuclear p65 phosphorylation, and the DNA binding activity of NF-κB.
T16 1218-1306 Sentence denotes In contrast, PTX markedly enhanced the phosphorylation and DNA binding activity of CREB.
T17 1307-1441 Sentence denotes Cells concomitantly treated with PTX and LPS secreted similar levels of TNF-α in the presence and absence Protein kinase A inhibition.
T18 1443-1453 Sentence denotes DISCUSSION
T19 1454-1727 Sentence denotes The increased level of cAMP that results from phosphodiesterase inhibition affects cytoplasmic and nuclear events, resulting in the attenuation of NF-κB and the activation of CREB transcriptional DNA binding through pathways that are partially Protein kinase A-independent.
T20 1729-1739 Sentence denotes CONCLUSION
T21 1740-1924 Sentence denotes PTX-mediated phosphodiesterase inhibition occurs partially through a Protein kinase A-independent pathway and may serve as a useful tool in the attenuation of LPS-induced inflammation.
T22 1927-1939 Sentence denotes INTRODUCTION
T23 1940-2127 Sentence denotes The bacterial membrane component lipopolysaccharide (LPS) is capable of initiating phosphorylation and activation of multiple host intracellular protein kinases and transcription factors.
T24 2128-2314 Sentence denotes Transcription factor activation, which results in the modulation of gene transcription and protein synthesis, is a critical element in the defense mechanism of the host immune system.1,2
T25 2315-2538 Sentence denotes LPS-induced transcription factor activation has been shown to be a key regulator of tumor necrosis factor-α (TNF-α) production.3 TNF-α is a potent pro-inflammatory cytokine involved in a wide spectrum of cellular responses.
T26 2539-2883 Sentence denotes Furthermore, TNF-α synthesis can be attenuated in immune cells exposed to phosphodiesterase (PDE) inhibition after challenge by a variety of pro-inflammatory stimulants.4 The signaling mechanisms affected by PDE inhibition, which ultimately lead to the downregulation of TNF-α production, have not been well characterized in inflammatory cells.
T27 2884-3511 Sentence denotes Classically, it has been demonstrated that PDE inhibition results in the intracellular accumulation of the second messenger cyclic adenosine-3,5-monophosphate (cAMP) and subsequent activation of Protein kinase A (PKA).5 PKA activation then leads to the phosphorylation of the transcription factor cAMP-response element binding protein (CREB), transmission of signals into the nucleus, and the subsequent modulation of gene transcription.6 This apparently simple linear cascade does not fully explain the mechanism by which an elevation in the intracellular cAMP level exerts wide-ranging effects on multiple cellular functions.
T28 3512-3640 Sentence denotes There is a growing body of evidence suggesting that cAMP may function through both PKA-dependent and -independent mechanisms.6–8
T29 3641-3770 Sentence denotes LPS-induced activation of the transcription factor nuclear factor-κB (NF-κB) has also been the focus of a great deal of research.
T30 3771-3947 Sentence denotes It has been clearly demonstrated that agents that increase intracellular cAMP also inhibit NF-κB-dependent pro-inflammatory gene transcription, particularly of the TNF-α gene.9
T31 3948-4056 Sentence denotes Controversy exists regarding the exact mechanism(s) by which PDE inhibition down-regulates TNF-α production.
T32 4057-4322 Sentence denotes Possibilities include, but are not limited to, inhibition of NF-κB DNA binding activity, downregulation of NF-κB transcriptional activity, increased CREB activation, and competition between NF-κB and CREB for common co-activators such as CREB binding protein (CBP).
T33 4323-4407 Sentence denotes It is also not known whether these processes rely solely upon the activation of PKA.
T34 4408-4640 Sentence denotes Therefore, the objective of the present study is to determine the effects of nonspecific PDE inhibition with 1-[5-oxohexyl]-3,7-dimethylxanthine (Pentoxifylline; PTX) on NF-κB and CREB activation in vitro in human mononuclear cells.
T35 4641-4747 Sentence denotes With the use of specific inhibitors, we also investigated the role of PKA in LPS-induced TNF-α production.
T36 4749-4770 Sentence denotes MATERIALS AND METHODS
T37 4771-4872 Sentence denotes This study was approved by the Human Research Protections Program and the Institutional Review Board.
T38 4873-4974 Sentence denotes Written consent to participate in the study was obtained from all volunteers prior to blood donation.
T39 4975-5051 Sentence denotes Heparinized Vacutainers were purchased from Becton Dickinson (San Jose, CA).

events-check-again

Id Subject Object Predicate Lexical cue Negation Speculation
T887 32-38 Regulation denotes effect true
T888 122-149 Protein denotes tumor necrosis factor-alpha
T889 151-156 Protein denotes TNF-α
T890 158-168 Gene_expression denotes production
T891 251-261 Gene_expression denotes production
T892 265-270 Protein denotes TNF-α
T893 271-280 Positive_regulation denotes following
T894 411-417 Regulation denotes alters
T895 418-423 Protein denotes TNF-α
T896 424-434 Gene_expression denotes production
T897 435-453 Positive_regulation denotes in the presence of
T898 667-681 Phosphorylation denotes phosphorylated
T899 694-699 Protein denotes I-κBα
T900 719-722 Protein denotes p65
T901 888-893 Protein denotes TNF-α
T902 1108-1114 Negative_regulation denotes reduce
T903 1108-1114 Negative_regulation denotes reduce
T904 1127-1132 Protein denotes I-κBα
T905 1133-1148 Phosphorylation denotes phosphorylation
T906 1158-1161 Protein denotes p65
T907 1162-1177 Phosphorylation denotes phosphorylation
T908 1352-1360 Localization denotes secreted
T909 1379-1384 Protein denotes TNF-α
T910 1392-1400 Regulation denotes presence
T911 1405-1412 Regulation denotes absence true
T2369 2386-2395 Regulation denotes regulator
T2370 2399-2422 Protein denotes tumor necrosis factor-α
T2371 2424-2429 Protein denotes TNF-α
T2372 2431-2441 Gene_expression denotes production
T2373 2444-2449 Protein denotes TNF-α
T2374 2552-2557 Protein denotes TNF-α
T2375 2558-2567 Gene_expression denotes synthesis
T2376 2575-2585 Negative_regulation denotes attenuated
T2377 2780-2784 Positive_regulation denotes lead
T2378 2792-2806 Negative_regulation denotes downregulation
T2379 2810-2815 Protein denotes TNF-α
T2380 2816-2826 Gene_expression denotes production
T2381 3854-3861 Negative_regulation denotes inhibit
T2382 3868-3877 Regulation denotes dependent
T2383 3900-3913 Transcription denotes transcription
T2384 3935-3940 Protein denotes TNF-α
T2385 4024-4038 Negative_regulation denotes down-regulates
T2386 4039-4044 Protein denotes TNF-α
T2387 4045-4055 Gene_expression denotes production
T2388 4703-4707 Regulation denotes role true
T2389 4722-4729 Positive_regulation denotes induced
T2390 4730-4735 Protein denotes TNF-α
T2391 4736-4746 Gene_expression denotes production
R650 T888 T890 themeOf tumor necrosis factor-alpha,production
R651 T890 T887 themeOf production,effect
R652 T891 T893 themeOf production,following
R653 T892 T891 themeOf TNF-α,production
R654 T894 T897 themeOf alters,in the presence of
R655 T895 T896 themeOf TNF-α,production
R656 T896 T894 themeOf production,alters
R657 T899 T898 themeOf I-κBα,phosphorylated
R658 T904 T905 themeOf I-κBα,phosphorylation
R659 T905 T903 themeOf phosphorylation,reduce
R660 T906 T907 themeOf p65,phosphorylation
R661 T907 T902 themeOf phosphorylation,reduce
R662 T908 T910 themeOf secreted,presence
R663 T908 T911 themeOf secreted,absence
R664 T909 T908 themeOf TNF-α,secreted
R1831 T2370 T2372 themeOf tumor necrosis factor-α,production
R1832 T2371 T2370 equivalentTo TNF-α,tumor necrosis factor-α
R1833 T2372 T2369 themeOf production,regulator
R1834 T2374 T2375 themeOf TNF-α,synthesis
R1836 T2375 T2376 themeOf synthesis,attenuated
R1838 T2378 T2377 themeOf downregulation,lead
R1839 T2379 T2380 themeOf TNF-α,production
R1840 T2380 T2378 themeOf production,downregulation
R1842 T2382 T2381 themeOf dependent,inhibit
R1843 T2383 T2382 themeOf transcription,dependent
R1845 T2384 T2383 themeOf TNF-α,transcription
R1846 T2386 T2387 themeOf TNF-α,production
R1848 T2387 T2385 themeOf production,down-regulates
R1849 T2389 T2388 themeOf induced,role
R1850 T2390 T2391 themeOf TNF-α,production
R1853 T2391 T2389 themeOf production,induced

bionlp-st-ge-2016-reference-tees

Id Subject Object Predicate Lexical cue
T919 122-149 Protein denotes tumor necrosis factor-alpha
T920 151-156 Protein denotes TNF-α
T921 158-168 Gene_expression denotes production
T922 158-168 Gene_expression denotes production
T923 107-117 Positive_regulation denotes activation
T924 107-117 Positive_regulation denotes activation
T925 32-38 Regulation denotes effect
T926 32-38 Regulation denotes effect
T927 265-270 Protein denotes TNF-α
T928 251-261 Gene_expression denotes production
T929 285-296 Positive_regulation denotes stimulation
T930 418-423 Protein denotes TNF-α
T931 424-434 Gene_expression denotes production
T932 411-417 Regulation denotes alters
T933 667-699 Protein denotes phosphorylated cytoplasmic I-κBα
T934 701-718 Protein denotes nuclear factor-κB
T935 719-722 Protein denotes p65
T936 724-729 Protein denotes NF-κB
T937 736-781 Protein denotes nuclear cAMP-response element binding protein
T938 783-787 Protein denotes CREB
T939 819-824 Protein denotes NF-κB
T940 829-833 Protein denotes CREB
T941 808-815 Binding denotes binding
T942 808-815 Binding denotes binding
T943 888-893 Protein denotes TNF-α
T944 984-1000 Protein denotes Protein kinase A
T945 1001-1011 Negative_regulation denotes inhibition
T946 1070-1073 Protein denotes PTX
T947 1115-1128 Protein denotes cytoplasmic I
T948 1129-1132 Protein denotes κBα
T949 1158-1161 Protein denotes p65
T950 1211-1216 Protein denotes NF-κB
T951 1133-1148 Phosphorylation denotes phosphorylation
T952 1133-1148 Phosphorylation denotes phosphorylation
T953 1150-1157 Entity denotes nuclear
T954 1162-1177 Phosphorylation denotes phosphorylation
T955 1191-1198 Binding denotes binding
T956 1108-1114 Negative_regulation denotes reduce
T957 1231-1234 Protein denotes PTX
T958 1301-1305 Protein denotes CREB
T959 1257-1272 Phosphorylation denotes phosphorylation
T960 1244-1252 Positive_regulation denotes enhanced
T961 1340-1343 Protein denotes PTX
T962 1379-1384 Protein denotes TNF-α
T963 1413-1429 Protein denotes Protein kinase A
T964 1352-1360 Localization denotes secreted
T965 1352-1360 Localization denotes secreted
T966 1430-1440 Negative_regulation denotes inhibition
T967 1601-1606 Protein denotes NF-κB
T968 1629-1633 Protein denotes CREB
T969 1654-1661 Binding denotes binding
T970 1615-1625 Positive_regulation denotes activation
T971 1740-1743 Protein denotes PTX
T972 1809-1825 Protein denotes Protein kinase A
T2232 2057-2126 Protein denotes multiple host intracellular protein kinases and transcription factors
T2233 2023-2038 Phosphorylation denotes phosphorylation
T2234 2043-2053 Positive_regulation denotes activation
T2235 2012-2022 Positive_regulation denotes initiating
T2236 2012-2022 Positive_regulation denotes initiating
T2237 2399-2422 Protein denotes tumor necrosis factor-α
T2238 2424-2429 Protein denotes TNF-α
T2239 2444-2449 Protein denotes TNF-α
T2240 2386-2395 Regulation denotes regulator
T2241 2386-2395 Regulation denotes regulator
T2242 2552-2557 Protein denotes TNF-α
T2243 2632-2635 Protein denotes PDE
T2244 2810-2815 Protein denotes TNF-α
T2245 2613-2630 Protein denotes phosphodiesterase
T2246 2558-2567 Gene_expression denotes synthesis
T2247 2575-2585 Negative_regulation denotes attenuated
T2248 2637-2647 Negative_regulation denotes inhibition
T2249 2637-2647 Negative_regulation denotes inhibition
T2250 2816-2826 Gene_expression denotes production
T2251 2792-2806 Negative_regulation denotes downregulation
T2252 3079-3095 Protein denotes Protein kinase A
T2253 3097-3100 Protein denotes PKA
T2254 3104-3107 Protein denotes PKA
T2255 3181-3218 Protein denotes cAMP-response element binding protein
T2256 3220-3224 Protein denotes CREB
T2257 2971-2983 Positive_regulation denotes accumulation
T2258 3065-3075 Positive_regulation denotes activation
T2259 3108-3118 Positive_regulation denotes activation
T2260 3108-3118 Positive_regulation denotes activation
T2261 3124-3129 Positive_regulation denotes leads
T2262 3124-3129 Positive_regulation denotes leads
T2263 3137-3152 Phosphorylation denotes phosphorylation
T2264 3137-3152 Phosphorylation denotes phosphorylation
T2265 2942-2949 Positive_regulation denotes results
T2266 3595-3598 Protein denotes PKA
T2267 3671-3709 Protein denotes transcription factor nuclear factor-κB
T2268 3711-3716 Protein denotes NF-κB
T2269 3653-3663 Positive_regulation denotes activation
T2270 3653-3663 Positive_regulation denotes activation
T2271 3862-3867 Protein denotes NF-κB
T2272 3935-3940 Protein denotes TNF-α
T2273 3900-3913 Transcription denotes transcription
T2274 3900-3913 Transcription denotes transcription
T2275 3854-3861 Negative_regulation denotes inhibit
T2276 3854-3861 Negative_regulation denotes inhibit
T2277 4009-4012 Protein denotes PDE
T2278 4039-4044 Protein denotes TNF-α
T2279 4013-4023 Negative_regulation denotes inhibition
T2280 4045-4055 Gene_expression denotes production
T2281 4024-4038 Negative_regulation denotes down-regulates
T2282 4118-4123 Protein denotes NF-κB
T2283 4164-4169 Protein denotes NF-κB
T2284 4206-4210 Protein denotes CREB
T2285 4247-4252 Protein denotes NF-κB
T2286 4257-4261 Protein denotes CREB
T2287 4295-4315 Protein denotes CREB binding protein
T2288 4317-4320 Protein denotes CBP
T2289 4128-4135 Binding denotes binding
T2290 4211-4221 Positive_regulation denotes activation
T2291 4227-4238 Binding denotes competition
T2292 4104-4114 Negative_regulation denotes inhibition
T2293 4403-4406 Protein denotes PKA
T2294 4389-4399 Positive_regulation denotes activation
T2295 4578-4583 Protein denotes NF-κB
T2296 4588-4592 Protein denotes CREB
T2297 4593-4603 Positive_regulation denotes activation
T2298 4593-4603 Positive_regulation denotes activation
T2299 4711-4714 Protein denotes PKA
T2300 4730-4735 Protein denotes TNF-α
T2301 4736-4746 Gene_expression denotes production
T2302 4703-4707 Positive_regulation denotes role
T2303 4718-4729 Positive_regulation denotes LPS-induced
R669 T919 T921 themeOf tumor necrosis factor-alpha,production
R670 T920 T922 themeOf TNF-α,production
R671 T921 T923 themeOf production,activation
R672 T922 T924 themeOf production,activation
R673 T923 T925 themeOf activation,effect
R674 T924 T926 themeOf activation,effect
R675 T927 T928 themeOf TNF-α,production
R676 T928 T929 themeOf production,stimulation
R677 T930 T931 themeOf TNF-α,production
R678 T931 T932 themeOf production,alters
R679 T939 T941 themeOf NF-κB,binding
R680 T940 T942 themeOf CREB,binding
R681 T944 T945 themeOf Protein kinase A,inhibition
R682 T946 T956 causeOf PTX,reduce
R683 T947 T951 themeOf cytoplasmic I,phosphorylation
R684 T948 T952 themeOf κBα,phosphorylation
R685 T949 T954 themeOf p65,phosphorylation
R686 T950 T955 themeOf NF-κB,binding
R687 T953 T954 Site nuclear,phosphorylation
R688 T954 T956 themeOf phosphorylation,reduce
R689 T957 T960 causeOf PTX,enhanced
R690 T958 T959 themeOf CREB,phosphorylation
R691 T959 T960 themeOf phosphorylation,enhanced
R692 T961 T964 themeOf PTX,secreted
R693 T962 T965 themeOf TNF-α,secreted
R694 T963 T966 themeOf Protein kinase A,inhibition
R695 T967 T969 themeOf NF-κB,binding
R696 T969 T970 themeOf binding,activation
R1748 T2232 T2233 themeOf multiple host intracellular protein kinases and transcription factors,phosphorylation
R1749 T2233 T2234 themeOf phosphorylation,activation
R1750 T2233 T2235 themeOf phosphorylation,initiating
R1751 T2234 T2236 themeOf activation,initiating
R1752 T2237 T2240 themeOf tumor necrosis factor-α,regulator
R1753 T2238 T2241 themeOf TNF-α,regulator
R1754 T2242 T2246 themeOf TNF-α,synthesis
R1755 T2243 T2248 themeOf PDE,inhibition
R1756 T2244 T2250 themeOf TNF-α,production
R1757 T2245 T2249 themeOf phosphodiesterase,inhibition
R1758 T2246 T2247 themeOf synthesis,attenuated
R1759 T2250 T2251 themeOf production,downregulation
R1760 T2280 T2281 themeOf production,down-regulates
R1761 T2252 T2257 themeOf Protein kinase A,accumulation
R1762 T2282 T2289 themeOf NF-κB,binding
R1763 T2253 T2259 themeOf PKA,activation
R1764 T2284 T2290 themeOf CREB,activation
R1765 T2285 T2291 themeOf NF-κB,competition
R1766 T2286 T2291 themeOf CREB,competition
R1767 T2289 T2292 themeOf binding,inhibition
R1768 T2254 T2260 themeOf PKA,activation
R1769 T2255 T2263 themeOf cAMP-response element binding protein,phosphorylation
R1770 T2293 T2294 themeOf PKA,activation
R1771 T2256 T2264 themeOf CREB,phosphorylation
R1772 T2295 T2297 themeOf NF-κB,activation
R1773 T2296 T2298 themeOf CREB,activation
R1774 T2257 T2258 themeOf accumulation,activation
R1775 T2258 T2265 themeOf activation,results
R1776 T2299 T2302 causeOf PKA,role
R1777 T2300 T2301 themeOf TNF-α,production
R1778 T2301 T2302 themeOf production,role
R1779 T2301 T2303 themeOf production,LPS-induced
R1780 T2259 T2261 themeOf activation,leads
R1781 T2260 T2262 themeOf activation,leads
R1782 T2267 T2269 themeOf transcription factor nuclear factor-κB,activation
R1783 T2268 T2270 themeOf NF-κB,activation
R1784 T2271 T2273 themeOf NF-κB,transcription
R1785 T2272 T2274 themeOf TNF-α,transcription
R1787 T2272 T2275 causeOf TNF-α,inhibit
R1788 T2272 T2276 causeOf TNF-α,inhibit
R1789 T2273 T2275 themeOf transcription,inhibit
R1791 T2274 T2276 themeOf transcription,inhibit
R1792 T2277 T2279 themeOf PDE,inhibition
R1794 T2278 T2280 themeOf TNF-α,production
R1796 T2279 T2281 causeOf inhibition,down-regulates

bionlp-st-ge-2016-uniprot

Id Subject Object Predicate Lexical cue
T759 122-143 P01375 denotes tumor necrosis factor
T760 151-154 P01375 denotes TNF
T761 151-156 P01375 denotes TNF-α
T762 265-268 P01375 denotes TNF
T763 265-270 P01375 denotes TNF-α
T764 418-421 P01375 denotes TNF
T765 418-423 P01375 denotes TNF-α
T766 719-722 P21579 denotes p65
T767 719-722 Q04206 denotes p65
T768 744-781 O43889 denotes cAMP-response element binding protein
T769 744-781 P15336 denotes cAMP-response element binding protein
T770 744-781 P18848 denotes cAMP-response element binding protein
T771 744-781 Q8TEY5 denotes cAMP-response element binding protein
T772 744-781 Q02930 denotes cAMP-response element binding protein
T773 744-781 P16220 denotes cAMP-response element binding protein
T774 783-787 P16220 denotes CREB
T775 783-787 O43889 denotes CREB
T776 783-787 Q8TEY5 denotes CREB
T777 783-787 Q02930 denotes CREB
T778 783-787 P18848 denotes CREB
T779 783-787 P15336 denotes CREB
T780 829-833 O43889 denotes CREB
T781 829-833 Q02930 denotes CREB
T782 829-833 P15336 denotes CREB
T783 829-833 P16220 denotes CREB
T784 829-833 Q8TEY5 denotes CREB
T785 829-833 P18848 denotes CREB
T786 888-891 P01375 denotes TNF
T787 888-893 P01375 denotes TNF-α
T788 1158-1161 Q04206 denotes p65
T789 1158-1161 P21579 denotes p65
T790 1301-1305 O43889 denotes CREB
T791 1301-1305 Q8TEY5 denotes CREB
T792 1301-1305 Q02930 denotes CREB
T793 1301-1305 P18848 denotes CREB
T794 1301-1305 P16220 denotes CREB
T795 1301-1305 P15336 denotes CREB
T796 1379-1382 P01375 denotes TNF
T797 1379-1384 P01375 denotes TNF-α
T798 1629-1633 P16220 denotes CREB
T799 1629-1633 P18848 denotes CREB
T800 1629-1633 Q02930 denotes CREB
T801 1629-1633 P15336 denotes CREB
T802 1629-1633 Q8TEY5 denotes CREB
T803 1629-1633 O43889 denotes CREB
T2041 2105-2148 Q02548 denotes transcription factors. Transcription factor
T2042 2105-2148 Q9UL17 denotes transcription factors. Transcription factor
T2043 2399-2420 P01375 denotes tumor necrosis factor
T2044 2424-2427 P01375 denotes TNF
T2045 2424-2429 P01375 denotes TNF-α
T2046 2444-2447 P01375 denotes TNF
T2047 2444-2449 P01375 denotes TNF-α
T2048 2552-2555 P01375 denotes TNF
T2049 2552-2557 P01375 denotes TNF-α
T2050 2810-2813 P01375 denotes TNF
T2051 2810-2815 P01375 denotes TNF-α
T2052 3181-3218 P15336 denotes cAMP-response element binding protein
T2053 3181-3218 Q02930 denotes cAMP-response element binding protein
T2054 3181-3218 P16220 denotes cAMP-response element binding protein
T2055 3181-3218 O43889 denotes cAMP-response element binding protein
T2056 3181-3218 P18848 denotes cAMP-response element binding protein
T2057 3181-3218 Q8TEY5 denotes cAMP-response element binding protein
T2058 3220-3224 Q8TEY5 denotes CREB
T2059 3220-3224 P15336 denotes CREB
T2060 3220-3224 P16220 denotes CREB
T2061 3220-3224 P18848 denotes CREB
T2062 3220-3224 Q02930 denotes CREB
T2063 3220-3224 O43889 denotes CREB
T2064 3935-3938 P01375 denotes TNF
T2065 3935-3940 P01375 denotes TNF-α
T2066 4039-4042 P01375 denotes TNF
T2067 4039-4044 P01375 denotes TNF-α
T2068 4206-4210 O43889 denotes CREB
T2069 4206-4210 P15336 denotes CREB
T2070 4206-4210 P16220 denotes CREB
T2071 4206-4210 Q8TEY5 denotes CREB
T2072 4206-4210 P18848 denotes CREB
T2073 4206-4210 Q02930 denotes CREB
T2074 4257-4261 O43889 denotes CREB
T2075 4257-4261 Q8TEY5 denotes CREB
T2076 4257-4261 P15336 denotes CREB
T2077 4257-4261 P16220 denotes CREB
T2078 4257-4261 P18848 denotes CREB
T2079 4257-4261 Q02930 denotes CREB
T2080 4295-4299 P16220 denotes CREB
T2081 4295-4299 P15336 denotes CREB
T2082 4295-4299 P18848 denotes CREB
T2083 4295-4299 Q8TEY5 denotes CREB
T2084 4295-4299 O43889 denotes CREB
T2085 4295-4299 Q02930 denotes CREB
T2086 4295-4315 Q92793 denotes CREB binding protein
T2087 4317-4320 Q92793 denotes CBP
T2088 4588-4592 P15336 denotes CREB
T2089 4588-4592 Q02930 denotes CREB
T2090 4588-4592 P16220 denotes CREB
T2091 4588-4592 Q8TEY5 denotes CREB
T2092 4588-4592 P18848 denotes CREB
T2093 4588-4592 O43889 denotes CREB
T2094 4730-4733 P01375 denotes TNF
T2095 4730-4735 P01375 denotes TNF-α
T2038 2101-2148 Q9NY61 denotes and transcription factors. Transcription factor
T2039 2105-2141 Q99853 denotes transcription factors. Transcription
T2040 2105-2141 Q9UL17 denotes transcription factors. Transcription

test2

Id Subject Object Predicate Lexical cue Negation Speculation
T32 122-149 Protein denotes tumor necrosis factor-alpha
T33 151-156 Protein denotes TNF-α
T34 158-168 Gene_expression denotes production
T35 251-261 Gene_expression denotes production
T36 265-270 Protein denotes TNF-α
T37 271-280 Positive_regulation denotes following
T38 411-417 Regulation denotes alters
T39 418-423 Protein denotes TNF-α
T40 424-434 Gene_expression denotes production
T41 667-681 Phosphorylation denotes phosphorylated
T42 694-699 Protein denotes I-κBα
T43 719-722 Protein denotes p65
T44 888-893 Protein denotes TNF-α
T45 1108-1114 Negative_regulation denotes reduce true
T46 1127-1132 Protein denotes I-κBα
T47 1133-1148 Phosphorylation denotes phosphorylation
T48 1158-1161 Protein denotes p65
T49 1162-1177 Phosphorylation denotes phosphorylation
T50 1191-1198 Binding denotes binding
T51 1244-1252 Positive_regulation denotes enhanced
T52 1352-1360 Gene_expression denotes secreted
T53 1379-1384 Protein denotes TNF-α
T1103 2386-2395 Regulation denotes regulator
T1104 2399-2422 Protein denotes tumor necrosis factor-α
T1105 2424-2429 Protein denotes TNF-α
T1106 2431-2441 Gene_expression denotes production
T1107 2444-2449 Protein denotes TNF-α
T1108 2552-2557 Protein denotes TNF-α
T1109 2558-2567 Gene_expression denotes synthesis
T1110 2575-2585 Negative_regulation denotes attenuated
T1111 2792-2806 Negative_regulation denotes downregulation
T1112 2810-2815 Protein denotes TNF-α
T1113 2816-2826 Gene_expression denotes production
T1114 3854-3861 Negative_regulation denotes inhibit
T1115 3868-3877 Regulation denotes dependent true
T1116 3935-3940 Protein denotes TNF-α
T1117 4013-4023 Negative_regulation denotes inhibition
T1118 4024-4038 Negative_regulation denotes down-regulates
T1119 4039-4044 Protein denotes TNF-α
T1120 4045-4055 Gene_expression denotes production
T1121 4703-4707 Regulation denotes role
T1122 4722-4729 Positive_regulation denotes induced
T1123 4730-4735 Protein denotes TNF-α
T1124 4736-4746 Gene_expression denotes production
R20 T32 T34 themeOf tumor necrosis factor-alpha,production
R21 T35 T37 themeOf production,following
R22 T36 T35 themeOf TNF-α,production
R23 T39 T40 themeOf TNF-α,production
R24 T40 T38 themeOf production,alters
R25 T42 T41 themeOf I-κBα,phosphorylated
R26 T46 T47 themeOf I-κBα,phosphorylation
R27 T47 T45 themeOf phosphorylation,reduce
R28 T48 T49 themeOf p65,phosphorylation
R29 T48 T50 themeOf p65,binding
R30 T49 T45 themeOf phosphorylation,reduce
R31 T50 T45 themeOf binding,reduce
R32 T53 T52 themeOf TNF-α,secreted
R820 T1104 T1106 themeOf tumor necrosis factor-α,production
R821 T1105 T1104 equivalentTo TNF-α,tumor necrosis factor-α
R822 T1106 T1103 themeOf production,regulator
R823 T1108 T1109 themeOf TNF-α,synthesis
R824 T1109 T1110 themeOf synthesis,attenuated
R825 T1112 T1113 themeOf TNF-α,production
R826 T1113 T1111 themeOf production,downregulation
R827 T1115 T1114 themeOf dependent,inhibit
R828 T1119 T1120 themeOf TNF-α,production
R829 T1120 T1118 themeOf production,down-regulates
R830 T1123 T1124 themeOf TNF-α,production
R831 T1124 T1122 themeOf production,induced