PubMed:10080532
Annnotations
jnlpba-st-training
{"project":"jnlpba-st-training","denotations":[{"id":"T1","span":{"begin":14,"end":18},"obj":"protein"},{"id":"T2","span":{"begin":48,"end":63},"obj":"cell_type"},{"id":"T3","span":{"begin":67,"end":97},"obj":"protein"},{"id":"T4","span":{"begin":103,"end":121},"obj":"protein"},{"id":"T5","span":{"begin":123,"end":136},"obj":"protein"},{"id":"T6","span":{"begin":138,"end":142},"obj":"protein"},{"id":"T7","span":{"begin":148,"end":162},"obj":"protein"},{"id":"T8","span":{"begin":164,"end":169},"obj":"protein"},{"id":"T9","span":{"begin":223,"end":238},"obj":"cell_type"},{"id":"T10","span":{"begin":250,"end":263},"obj":"protein"},{"id":"T11","span":{"begin":265,"end":269},"obj":"protein"},{"id":"T12","span":{"begin":272,"end":287},"obj":"protein"},{"id":"T13","span":{"begin":289,"end":313},"obj":"protein"},{"id":"T14","span":{"begin":315,"end":321},"obj":"protein"},{"id":"T15","span":{"begin":328,"end":361},"obj":"protein"},{"id":"T16","span":{"begin":363,"end":368},"obj":"protein"},{"id":"T17","span":{"begin":371,"end":389},"obj":"protein"},{"id":"T18","span":{"begin":391,"end":400},"obj":"protein"},{"id":"T19","span":{"begin":405,"end":413},"obj":"protein"},{"id":"T20","span":{"begin":419,"end":437},"obj":"protein"},{"id":"T21","span":{"begin":439,"end":448},"obj":"protein"},{"id":"T22","span":{"begin":486,"end":490},"obj":"protein"},{"id":"T23","span":{"begin":495,"end":500},"obj":"protein"},{"id":"T24","span":{"begin":534,"end":538},"obj":"protein"},{"id":"T25","span":{"begin":630,"end":650},"obj":"protein"},{"id":"T26","span":{"begin":652,"end":657},"obj":"protein"},{"id":"T27","span":{"begin":659,"end":709},"obj":"protein"},{"id":"T28","span":{"begin":767,"end":776},"obj":"cell_type"},{"id":"T29","span":{"begin":819,"end":842},"obj":"protein"},{"id":"T30","span":{"begin":852,"end":856},"obj":"protein"},{"id":"T31","span":{"begin":857,"end":862},"obj":"protein"},{"id":"T32","span":{"begin":957,"end":962},"obj":"protein"},{"id":"T33","span":{"begin":979,"end":1002},"obj":"protein"},{"id":"T34","span":{"begin":1014,"end":1018},"obj":"protein"},{"id":"T35","span":{"begin":1019,"end":1024},"obj":"protein"},{"id":"T36","span":{"begin":1033,"end":1038},"obj":"protein"},{"id":"T37","span":{"begin":1098,"end":1107},"obj":"cell_type"},{"id":"T38","span":{"begin":1116,"end":1120},"obj":"protein"},{"id":"T39","span":{"begin":1148,"end":1159},"obj":"cell_type"},{"id":"T40","span":{"begin":1175,"end":1180},"obj":"protein"},{"id":"T41","span":{"begin":1240,"end":1243},"obj":"protein"},{"id":"T42","span":{"begin":1268,"end":1272},"obj":"protein"},{"id":"T43","span":{"begin":1438,"end":1447},"obj":"cell_type"},{"id":"T44","span":{"begin":1451,"end":1454},"obj":"protein"},{"id":"T45","span":{"begin":1489,"end":1506},"obj":"protein"},{"id":"T46","span":{"begin":1544,"end":1569},"obj":"protein"},{"id":"T47","span":{"begin":1608,"end":1613},"obj":"protein"},{"id":"T48","span":{"begin":1617,"end":1621},"obj":"protein"},{"id":"T49","span":{"begin":1626,"end":1631},"obj":"protein"},{"id":"T50","span":{"begin":1641,"end":1646},"obj":"protein"},{"id":"T51","span":{"begin":1685,"end":1689},"obj":"protein"},{"id":"T52","span":{"begin":1690,"end":1695},"obj":"protein"},{"id":"T53","span":{"begin":1736,"end":1744},"obj":"protein"},{"id":"T54","span":{"begin":1749,"end":1758},"obj":"protein"},{"id":"T55","span":{"begin":1770,"end":1775},"obj":"protein"},{"id":"T56","span":{"begin":1817,"end":1821},"obj":"protein"},{"id":"T57","span":{"begin":1835,"end":1839},"obj":"protein"},{"id":"T58","span":{"begin":1840,"end":1845},"obj":"protein"}],"text":"Inhibition of IL-4-inducible gene expression in human monocytes by type I and type II interferons.\nThe Th2-type cytokines, interleukin-4 (IL-4) and interleukin-13 (IL-13), induce expression of a distinct subset of genes in human monocytes, including FcepsilonRIIb (CD23), 15-lipoxygenase, IL-1 receptor antagonist (IL-1ra), and type I and type II IL-1 receptors (IL-1R). Type I interferons (IFN-alpha and IFN-beta) and type II interferon (IFN-gamma) inhibit induction of these genes by IL-4 and IL-13. However, the mechanism by which IFNs mediate this inhibition has not been defined. In this overview, we discuss the role of the transcription factor, STAT6 (signal transducer and activator of transcription-6) in mediating IL-4- and IL-13-induced gene expression in monocytes. We also discuss our recent findings that type I and type II IFNs suppress IL-4/IL-13-inducible gene expression by inhibiting tyrosine phosphorylation and nuclear translocation of STAT6. The ability of type I and type II IFNs to inhibit IL-4/IL-13-induced STAT6 activity is dose- and time-dependent, and is not unique to monocytes because IFNs induce the same effects in fibroblasts. Inhibition of STAT6 activity is not evident unless cells are preincubated with IFN for at least 1 h before IL-4 stimulation. Furthermore, inhibition can be blocked by actinomycin D, indicating a requirement for de novo transcription. We propose a model in which stimulation of monocytes by IFN activates de novo synthesis of an inhibitory factor, possibly one or more members of the SOCS/ SSI/CIS gene family, capable of suppressing activation of STAT6 by IL-4 and IL-13. Because STAT6 activation plays an essential role in IL-4/IL-13-induced gene expression, the ability of IFN-beta and IFN-gamma to inhibit STAT6 activity provides an explanation for how IFNs can suppress IL-4/IL-13-inducible gene expression."}
genia-medco-coref
{"project":"genia-medco-coref","denotations":[{"id":"C1","span":{"begin":48,"end":63},"obj":"NP"},{"id":"C2","span":{"begin":67,"end":97},"obj":"NP"},{"id":"C3","span":{"begin":99,"end":121},"obj":"NP"},{"id":"C4","span":{"begin":123,"end":170},"obj":"NP"},{"id":"C6","span":{"begin":223,"end":238},"obj":"NP"},{"id":"C5","span":{"begin":193,"end":369},"obj":"NP"},{"id":"C8","span":{"begin":419,"end":449},"obj":"NP"},{"id":"C7","span":{"begin":371,"end":449},"obj":"NP"},{"id":"C9","span":{"begin":471,"end":482},"obj":"NP"},{"id":"C10","span":{"begin":486,"end":500},"obj":"NP"},{"id":"C11","span":{"begin":511,"end":524},"obj":"NP"},{"id":"C12","span":{"begin":528,"end":533},"obj":"NP"},{"id":"C13","span":{"begin":534,"end":538},"obj":"NP"},{"id":"C14","span":{"begin":626,"end":650},"obj":"NP"},{"id":"C15","span":{"begin":652,"end":710},"obj":"NP"},{"id":"C16","span":{"begin":767,"end":776},"obj":"NP"},{"id":"C17","span":{"begin":794,"end":813},"obj":"NP"},{"id":"C18","span":{"begin":814,"end":818},"obj":"NP"},{"id":"C19","span":{"begin":819,"end":842},"obj":"NP"},{"id":"C20","span":{"begin":852,"end":888},"obj":"NP"},{"id":"C21","span":{"begin":957,"end":962},"obj":"NP"},{"id":"C22","span":{"begin":979,"end":1002},"obj":"NP"},{"id":"C23","span":{"begin":1098,"end":1107},"obj":"NP"},{"id":"C24","span":{"begin":1116,"end":1120},"obj":"NP"},{"id":"C25","span":{"begin":1175,"end":1189},"obj":"NP"},{"id":"C26","span":{"begin":1240,"end":1243},"obj":"NP"},{"id":"C27","span":{"begin":1406,"end":1413},"obj":"NP"},{"id":"C28","span":{"begin":1417,"end":1422},"obj":"NP"},{"id":"C29","span":{"begin":1438,"end":1447},"obj":"NP"},{"id":"C30","span":{"begin":1451,"end":1454},"obj":"NP"},{"id":"C32","span":{"begin":1608,"end":1613},"obj":"NP"},{"id":"C31","span":{"begin":1594,"end":1613},"obj":"NP"},{"id":"C33","span":{"begin":1617,"end":1631},"obj":"NP"},{"id":"C34","span":{"begin":1641,"end":1657},"obj":"NP"},{"id":"C35","span":{"begin":1685,"end":1719},"obj":"NP"},{"id":"C36","span":{"begin":1749,"end":1758},"obj":"NP"},{"id":"C37","span":{"begin":1770,"end":1784},"obj":"NP"},{"id":"C38","span":{"begin":1817,"end":1821},"obj":"NP"},{"id":"C39","span":{"begin":1835,"end":1871},"obj":"NP"}],"relations":[{"id":"R1","pred":"coref-appos","subj":"C4","obj":"C3"},{"id":"R2","pred":"coref-ident","subj":"C6","obj":"C1"},{"id":"R3","pred":"coref-ident","subj":"C7","obj":"C2"},{"id":"R4","pred":"coref-ident","subj":"C9","obj":"C5"},{"id":"R5","pred":"coref-ident","subj":"C10","obj":"C3"},{"id":"R6","pred":"coref-relat","subj":"C12","obj":"C11"},{"id":"R7","pred":"coref-ident","subj":"C13","obj":"C7"},{"id":"R8","pred":"coref-appos","subj":"C15","obj":"C14"},{"id":"R9","pred":"coref-ident","subj":"C16","obj":"C6"},{"id":"R10","pred":"coref-relat","subj":"C18","obj":"C17"},{"id":"R11","pred":"coref-ident","subj":"C19","obj":"C7"},{"id":"R12","pred":"coref-ident","subj":"C21","obj":"C14"},{"id":"R13","pred":"coref-ident","subj":"C22","obj":"C19"},{"id":"R14","pred":"coref-ident","subj":"C23","obj":"C16"},{"id":"R15","pred":"coref-ident","subj":"C24","obj":"C22"},{"id":"R16","pred":"coref-ident","subj":"C26","obj":"C24"},{"id":"R17","pred":"coref-relat","subj":"C28","obj":"C27"},{"id":"R18","pred":"coref-ident","subj":"C29","obj":"C23"},{"id":"R19","pred":"coref-ident","subj":"C30","obj":"C26"},{"id":"R20","pred":"coref-ident","subj":"C32","obj":"C21"},{"id":"R21","pred":"coref-ident","subj":"C33","obj":"C10"},{"id":"R22","pred":"coref-ident","subj":"C34","obj":"C31"},{"id":"R23","pred":"coref-ident","subj":"C35","obj":"C20"},{"id":"R24","pred":"coref-ident","subj":"C36","obj":"C8"},{"id":"R25","pred":"coref-ident","subj":"C37","obj":"C25"},{"id":"R26","pred":"coref-ident","subj":"C38","obj":"C30"},{"id":"R27","pred":"coref-ident","subj":"C39","obj":"C35"}],"text":"Inhibition of IL-4-inducible gene expression in human monocytes by type I and type II interferons.\nThe Th2-type cytokines, interleukin-4 (IL-4) and interleukin-13 (IL-13), induce expression of a distinct subset of genes in human monocytes, including FcepsilonRIIb (CD23), 15-lipoxygenase, IL-1 receptor antagonist (IL-1ra), and type I and type II IL-1 receptors (IL-1R). Type I interferons (IFN-alpha and IFN-beta) and type II interferon (IFN-gamma) inhibit induction of these genes by IL-4 and IL-13. However, the mechanism by which IFNs mediate this inhibition has not been defined. In this overview, we discuss the role of the transcription factor, STAT6 (signal transducer and activator of transcription-6) in mediating IL-4- and IL-13-induced gene expression in monocytes. We also discuss our recent findings that type I and type II IFNs suppress IL-4/IL-13-inducible gene expression by inhibiting tyrosine phosphorylation and nuclear translocation of STAT6. The ability of type I and type II IFNs to inhibit IL-4/IL-13-induced STAT6 activity is dose- and time-dependent, and is not unique to monocytes because IFNs induce the same effects in fibroblasts. Inhibition of STAT6 activity is not evident unless cells are preincubated with IFN for at least 1 h before IL-4 stimulation. Furthermore, inhibition can be blocked by actinomycin D, indicating a requirement for de novo transcription. We propose a model in which stimulation of monocytes by IFN activates de novo synthesis of an inhibitory factor, possibly one or more members of the SOCS/ SSI/CIS gene family, capable of suppressing activation of STAT6 by IL-4 and IL-13. Because STAT6 activation plays an essential role in IL-4/IL-13-induced gene expression, the ability of IFN-beta and IFN-gamma to inhibit STAT6 activity provides an explanation for how IFNs can suppress IL-4/IL-13-inducible gene expression."}
semrep-sample
{"project":"semrep-sample","denotations":[{"id":"E1-ti-1","span":{"begin":14,"end":33},"obj":"cui:C1334119"},{"id":"E2-ti-1","span":{"begin":34,"end":44},"obj":"cui:C0185117"},{"id":"E3-ti-1","span":{"begin":48,"end":53},"obj":"cui:C0020114"},{"id":"E4-ti-1","span":{"begin":54,"end":63},"obj":"cui:C0026473"},{"id":"E5-ti-1","span":{"begin":67,"end":71},"obj":"cui:C1547052"},{"id":"E6-ti-1","span":{"begin":78,"end":97},"obj":"cui:C0021745"},{"id":"T1","span":{"begin":34,"end":44},"obj":"PART_OF"},{"id":"T2","span":{"begin":48,"end":63},"obj":"PART_OF"},{"id":"E1-ab-1","span":{"begin":107,"end":111},"obj":"cui:C1547052"},{"id":"E2-ab-1","span":{"begin":112,"end":121},"obj":"cui:C0079189"},{"id":"E3-ab-1","span":{"begin":123,"end":136},"obj":"cui:C0021758"},{"id":"E4-ab-1","span":{"begin":148,"end":162},"obj":"cui:C0214743"},{"id":"E5-ab-1","span":{"begin":179,"end":189},"obj":"cui:C0185117"},{"id":"E6-ab-1","span":{"begin":214,"end":219},"obj":"cui:C0017337"},{"id":"E7-ab-1","span":{"begin":223,"end":228},"obj":"cui:C0020114"},{"id":"E8-ab-1","span":{"begin":229,"end":238},"obj":"cui:C0026473"},{"id":"E9-ab-1","span":{"begin":265,"end":269},"obj":"cui:C0123242"},{"id":"E10-ab-1","span":{"begin":275,"end":287},"obj":"cui:C0023837"},{"id":"E11-ab-1","span":{"begin":289,"end":302},"obj":"cui:C0063710"},{"id":"E12-ab-1","span":{"begin":328,"end":332},"obj":"cui:C1547052"},{"id":"E13-ab-1","span":{"begin":339,"end":346},"obj":"cui:C0441730"},{"id":"E14-ab-1","span":{"begin":347,"end":361},"obj":"cui:C0063710"},{"id":"T3","span":{"begin":179,"end":189},"obj":"PART_OF"},{"id":"T4","span":{"begin":223,"end":238},"obj":"PART_OF"},{"id":"T5","span":{"begin":303,"end":313},"obj":"INHIBITS"},{"id":"E1-ab-2","span":{"begin":371,"end":375},"obj":"cui:C1547052"},{"id":"E2-ab-2","span":{"begin":378,"end":389},"obj":"cui:C0021747"},{"id":"E3-ab-2","span":{"begin":391,"end":400},"obj":"cui:C1610033"},{"id":"E4-ab-2","span":{"begin":405,"end":413},"obj":"cui:C0015980"},{"id":"E5-ab-2","span":{"begin":419,"end":437},"obj":"cui:C0021745"},{"id":"E6-ab-2","span":{"begin":439,"end":442},"obj":"cui:C0733470"},{"id":"E7-ab-2","span":{"begin":458,"end":467},"obj":"cui:C0857127"},{"id":"E8-ab-2","span":{"begin":477,"end":482},"obj":"cui:C0017337"},{"id":"E9-ab-2","span":{"begin":486,"end":490},"obj":"cui:C0021758"},{"id":"E10-ab-2","span":{"begin":495,"end":500},"obj":"cui:C0214743"},{"id":"T6","span":{"begin":378,"end":400},"obj":"ISA"},{"id":"T7","span":{"begin":378,"end":400},"obj":"ISA"},{"id":"T8","span":{"begin":378,"end":400},"obj":"ISA"},{"id":"T9","span":{"begin":458,"end":467},"obj":"STIMULATES"},{"id":"E1-ab-3","span":{"begin":515,"end":524},"obj":"cui:C0441712"},{"id":"E2-ab-3","span":{"begin":534,"end":538},"obj":"cui:C0733470"},{"id":"E3-ab-3","span":{"begin":567,"end":570},"obj":"cui:C1518422"},{"id":"E1-ab-4","span":{"begin":593,"end":601},"obj":"cui:C0814812"},{"id":"E2-ab-4","span":{"begin":618,"end":622},"obj":"cui:C0035820"},{"id":"E3-ab-4","span":{"begin":630,"end":650},"obj":"cui:C0040648"},{"id":"E4-ab-4","span":{"begin":652,"end":657},"obj":"cui:C1335877"},{"id":"E5-ab-4","span":{"begin":666,"end":676},"obj":"cui:C0040661"},{"id":"E6-ab-4","span":{"begin":694,"end":707},"obj":"cui:C0040649"},{"id":"E7-ab-4","span":{"begin":724,"end":728},"obj":"cui:C0021758"},{"id":"E8-ab-4","span":{"begin":740,"end":747},"obj":"cui:C0205263"},{"id":"E9-ab-4","span":{"begin":734,"end":752},"obj":"cui:C1334103"},{"id":"E10-ab-4","span":{"begin":753,"end":763},"obj":"cui:C0185117"},{"id":"E11-ab-4","span":{"begin":767,"end":776},"obj":"cui:C0026473"},{"id":"T10","span":{"begin":618,"end":622},"obj":"AFFECTS"},{"id":"T11","span":{"begin":618,"end":622},"obj":"AFFECTS"},{"id":"E1-ab-5","span":{"begin":798,"end":804},"obj":"cui:C0332185"},{"id":"E2-ab-5","span":{"begin":805,"end":813},"obj":"cui:C0243095"},{"id":"E3-ab-5","span":{"begin":819,"end":823},"obj":"cui:C1547052"},{"id":"E4-ab-5","span":{"begin":830,"end":837},"obj":"cui:C0441730"},{"id":"E5-ab-5","span":{"begin":838,"end":842},"obj":"cui:C0733470"},{"id":"E6-ab-5","span":{"begin":857,"end":877},"obj":"cui:C1334119"},{"id":"E7-ab-5","span":{"begin":878,"end":888},"obj":"cui:C0185117"},{"id":"E8-ab-5","span":{"begin":892,"end":902},"obj":"cui:C0311403"},{"id":"E9-ab-5","span":{"begin":903,"end":927},"obj":"cui:C1519726"},{"id":"E10-ab-5","span":{"begin":932,"end":953},"obj":"cui:C1518440"},{"id":"E11-ab-5","span":{"begin":957,"end":962},"obj":"cui:C1335877"},{"id":"T12","span":{"begin":843,"end":851},"obj":"INHIBITS"},{"id":"E1-ab-6","span":{"begin":968,"end":975},"obj":"cui:C0085732"},{"id":"E2-ab-6","span":{"begin":979,"end":983},"obj":"cui:C1547052"},{"id":"E3-ab-6","span":{"begin":990,"end":997},"obj":"cui:C0441730"},{"id":"E4-ab-6","span":{"begin":998,"end":1002},"obj":"cui:C0733470"},{"id":"E5-ab-6","span":{"begin":1019,"end":1024},"obj":"cui:C0214743"},{"id":"E6-ab-6","span":{"begin":1025,"end":1032},"obj":"cui:C0205263"},{"id":"E7-ab-6","span":{"begin":1033,"end":1038},"obj":"cui:C1335877"},{"id":"E8-ab-6","span":{"begin":1039,"end":1047},"obj":"cui:C0439167"},{"id":"E9-ab-6","span":{"begin":1051,"end":1055},"obj":"cui:C1446466"},{"id":"E10-ab-6","span":{"begin":1061,"end":1066},"obj":"cui:C0040223"},{"id":"E11-ab-6","span":{"begin":1084,"end":1087},"obj":"cui:C1518422"},{"id":"E12-ab-6","span":{"begin":1098,"end":1107},"obj":"cui:C0026473"},{"id":"E13-ab-6","span":{"begin":1116,"end":1120},"obj":"cui:C0733470"},{"id":"E14-ab-6","span":{"begin":1132,"end":1136},"obj":"cui:C0445247"},{"id":"E15-ab-6","span":{"begin":1137,"end":1144},"obj":"cui:C1280500"},{"id":"E16-ab-6","span":{"begin":1148,"end":1159},"obj":"cui:C0016030"},{"id":"T13","span":{"begin":1006,"end":1013},"obj":"INHIBITS"},{"id":"T14","span":{"begin":1145,"end":1147},"obj":"LOCATION_OF"},{"id":"E1-ab-7","span":{"begin":1175,"end":1180},"obj":"cui:C1335877"},{"id":"E2-ab-7","span":{"begin":1181,"end":1189},"obj":"cui:C0439167"},{"id":"E3-ab-7","span":{"begin":1193,"end":1196},"obj":"cui:C1518422"},{"id":"E4-ab-7","span":{"begin":1212,"end":1217},"obj":"cui:C0007634"},{"id":"E5-ab-7","span":{"begin":1240,"end":1243},"obj":"cui:C0733470"},{"id":"E6-ab-7","span":{"begin":1268,"end":1272},"obj":"cui:C0021758"},{"id":"E7-ab-7","span":{"begin":1273,"end":1284},"obj":"cui:C1292856"},{"id":"T15","span":{"begin":1235,"end":1239},"obj":"PART_OF"},{"id":"T16","span":{"begin":1273,"end":1284},"obj":"STIMULATES"},{"id":"E1-ab-8","span":{"begin":1328,"end":1341},"obj":"cui:C0010934"},{"id":"E2-ab-8","span":{"begin":1356,"end":1367},"obj":"cui:C1514873"},{"id":"E3-ab-8","span":{"begin":1372,"end":1379},"obj":"cui:C1515568"},{"id":"E4-ab-8","span":{"begin":1380,"end":1393},"obj":"cui:C0040649"},{"id":"E1-ab-9","span":{"begin":1408,"end":1413},"obj":"cui:C0026336"},{"id":"E2-ab-9","span":{"begin":1423,"end":1434},"obj":"cui:C1292856"},{"id":"E3-ab-9","span":{"begin":1438,"end":1447},"obj":"cui:C0026473"},{"id":"E4-ab-9","span":{"begin":1451,"end":1454},"obj":"cui:C0733470"},{"id":"E5-ab-9","span":{"begin":1465,"end":1472},"obj":"cui:C1515568"},{"id":"E6-ab-9","span":{"begin":1473,"end":1482},"obj":"cui:C0869032"},{"id":"E7-ab-9","span":{"begin":1489,"end":1499},"obj":"cui:C0243077"},{"id":"E8-ab-9","span":{"begin":1500,"end":1506},"obj":"cui:C1521761"},{"id":"E9-ab-9","span":{"begin":1508,"end":1516},"obj":"cui:C0332149"},{"id":"E10-ab-9","span":{"begin":1517,"end":1520},"obj":"cui:C0205447"},{"id":"E11-ab-9","span":{"begin":1524,"end":1528},"obj":"cui:C0205172"},{"id":"E12-ab-9","span":{"begin":1529,"end":1536},"obj":"cui:C0680022"},{"id":"E13-ab-9","span":{"begin":1544,"end":1548},"obj":"cui:C0299250"},{"id":"E14-ab-9","span":{"begin":1558,"end":1569},"obj":"cui:C1517488"},{"id":"E15-ab-9","span":{"begin":1582,"end":1593},"obj":"cui:C1260953"},{"id":"E16-ab-9","span":{"begin":1608,"end":1613},"obj":"cui:C1335877"},{"id":"E17-ab-9","span":{"begin":1617,"end":1621},"obj":"cui:C0021758"},{"id":"E18-ab-9","span":{"begin":1626,"end":1631},"obj":"cui:C0214743"},{"id":"T17","span":{"begin":1423,"end":1434},"obj":"AUGMENTS"},{"id":"T18","span":{"begin":1594,"end":1604},"obj":"STIMULATES"},{"id":"E1-ab-10","span":{"begin":1641,"end":1646},"obj":"cui:C1335877"},{"id":"E2-ab-10","span":{"begin":1667,"end":1676},"obj":"cui:C0205224"},{"id":"E3-ab-10","span":{"begin":1677,"end":1681},"obj":"cui:C0035820"},{"id":"E4-ab-10","span":{"begin":1696,"end":1703},"obj":"cui:C0205263"},{"id":"E5-ab-10","span":{"begin":1690,"end":1708},"obj":"cui:C1334103"},{"id":"E6-ab-10","span":{"begin":1709,"end":1719},"obj":"cui:C0185117"},{"id":"E7-ab-10","span":{"begin":1725,"end":1732},"obj":"cui:C0085732"},{"id":"E8-ab-10","span":{"begin":1736,"end":1744},"obj":"cui:C0015980"},{"id":"E9-ab-10","span":{"begin":1749,"end":1752},"obj":"cui:C0733470"},{"id":"E10-ab-10","span":{"begin":1770,"end":1775},"obj":"cui:C1335877"},{"id":"E11-ab-10","span":{"begin":1776,"end":1784},"obj":"cui:C0439167"},{"id":"E12-ab-10","span":{"begin":1797,"end":1808},"obj":"cui:C0681841"},{"id":"E13-ab-10","span":{"begin":1817,"end":1821},"obj":"cui:C0733470"},{"id":"E14-ab-10","span":{"begin":1840,"end":1860},"obj":"cui:C1334119"},{"id":"E15-ab-10","span":{"begin":1861,"end":1871},"obj":"cui:C0185117"},{"id":"T19","span":{"begin":1677,"end":1681},"obj":"INTERACTS_WITH"},{"id":"T20","span":{"begin":1826,"end":1834},"obj":"INHIBITS"}],"relations":[{"id":"R1","pred":"subjectOf","subj":"E1-ti-1","obj":"T1"},{"id":"R2","pred":"objectOf","subj":"E4-ti-1","obj":"T1"},{"id":"R3","pred":"subjectOf","subj":"E4-ti-1","obj":"T2"},{"id":"R4","pred":"objectOf","subj":"E3-ti-1","obj":"T2"},{"id":"R5","pred":"subjectOf","subj":"E6-ab-1","obj":"T3"},{"id":"R6","pred":"objectOf","subj":"E8-ab-1","obj":"T3"},{"id":"R7","pred":"subjectOf","subj":"E8-ab-1","obj":"T4"},{"id":"R8","pred":"objectOf","subj":"E7-ab-1","obj":"T4"},{"id":"R9","pred":"subjectOf","subj":"E10-ab-1","obj":"T5"},{"id":"R10","pred":"objectOf","subj":"E11-ab-1","obj":"T5"},{"id":"R11","pred":"subjectOf","subj":"E3-ab-2","obj":"T6"},{"id":"R12","pred":"objectOf","subj":"E2-ab-2","obj":"T6"},{"id":"R13","pred":"subjectOf","subj":"E5-ab-2","obj":"T7"},{"id":"R14","pred":"objectOf","subj":"E2-ab-2","obj":"T7"},{"id":"R15","pred":"subjectOf","subj":"E4-ab-2","obj":"T8"},{"id":"R16","pred":"objectOf","subj":"E2-ab-2","obj":"T8"},{"id":"R17","pred":"subjectOf","subj":"E9-ab-2","obj":"T9"},{"id":"R18","pred":"objectOf","subj":"E8-ab-2","obj":"T9"},{"id":"R19","pred":"subjectOf","subj":"E9-ab-4","obj":"T10"},{"id":"R20","pred":"objectOf","subj":"E11-ab-4","obj":"T10"},{"id":"R21","pred":"subjectOf","subj":"E7-ab-4","obj":"T11"},{"id":"R22","pred":"objectOf","subj":"E11-ab-4","obj":"T11"},{"id":"R23","pred":"subjectOf","subj":"E5-ab-5","obj":"T12"},{"id":"R24","pred":"objectOf","subj":"E6-ab-5","obj":"T12"},{"id":"R25","pred":"subjectOf","subj":"E4-ab-6","obj":"T13"},{"id":"R26","pred":"objectOf","subj":"E7-ab-6","obj":"T13"},{"id":"R27","pred":"subjectOf","subj":"E16-ab-6","obj":"T14"},{"id":"R28","pred":"objectOf","subj":"E13-ab-6","obj":"T14"},{"id":"R29","pred":"subjectOf","subj":"E5-ab-7","obj":"T15"},{"id":"R30","pred":"objectOf","subj":"E4-ab-7","obj":"T15"},{"id":"R31","pred":"subjectOf","subj":"E1-ab-7","obj":"T16"},{"id":"R32","pred":"objectOf","subj":"E6-ab-7","obj":"T16"},{"id":"R33","pred":"subjectOf","subj":"E4-ab-9","obj":"T17"},{"id":"R34","pred":"objectOf","subj":"E3-ab-9","obj":"T17"},{"id":"R35","pred":"subjectOf","subj":"E17-ab-9","obj":"T18"},{"id":"R36","pred":"objectOf","subj":"E16-ab-9","obj":"T18"},{"id":"R37","pred":"subjectOf","subj":"E8-ab-10","obj":"T19"},{"id":"R38","pred":"objectOf","subj":"E5-ab-10","obj":"T19"},{"id":"R39","pred":"subjectOf","subj":"E13-ab-10","obj":"T20"},{"id":"R40","pred":"objectOf","subj":"E14-ab-10","obj":"T20"}],"text":"Inhibition of IL-4-inducible gene expression in human monocytes by type I and type II interferons.\nThe Th2-type cytokines, interleukin-4 (IL-4) and interleukin-13 (IL-13), induce expression of a distinct subset of genes in human monocytes, including FcepsilonRIIb (CD23), 15-lipoxygenase, IL-1 receptor antagonist (IL-1ra), and type I and type II IL-1 receptors (IL-1R). Type I interferons (IFN-alpha and IFN-beta) and type II interferon (IFN-gamma) inhibit induction of these genes by IL-4 and IL-13. However, the mechanism by which IFNs mediate this inhibition has not been defined. In this overview, we discuss the role of the transcription factor, STAT6 (signal transducer and activator of transcription-6) in mediating IL-4- and IL-13-induced gene expression in monocytes. We also discuss our recent findings that type I and type II IFNs suppress IL-4/IL-13-inducible gene expression by inhibiting tyrosine phosphorylation and nuclear translocation of STAT6. The ability of type I and type II IFNs to inhibit IL-4/IL-13-induced STAT6 activity is dose- and time-dependent, and is not unique to monocytes because IFNs induce the same effects in fibroblasts. Inhibition of STAT6 activity is not evident unless cells are preincubated with IFN for at least 1 h before IL-4 stimulation. Furthermore, inhibition can be blocked by actinomycin D, indicating a requirement for de novo transcription. We propose a model in which stimulation of monocytes by IFN activates de novo synthesis of an inhibitory factor, possibly one or more members of the SOCS/ SSI/CIS gene family, capable of suppressing activation of STAT6 by IL-4 and IL-13. Because STAT6 activation plays an essential role in IL-4/IL-13-induced gene expression, the ability of IFN-beta and IFN-gamma to inhibit STAT6 activity provides an explanation for how IFNs can suppress IL-4/IL-13-inducible gene expression."}
pubmed-sentences-benchmark
{"project":"pubmed-sentences-benchmark","denotations":[{"id":"S1","span":{"begin":0,"end":98},"obj":"Sentence"},{"id":"S2","span":{"begin":99,"end":370},"obj":"Sentence"},{"id":"S3","span":{"begin":371,"end":501},"obj":"Sentence"},{"id":"S4","span":{"begin":502,"end":584},"obj":"Sentence"},{"id":"S5","span":{"begin":585,"end":777},"obj":"Sentence"},{"id":"S6","span":{"begin":778,"end":963},"obj":"Sentence"},{"id":"S7","span":{"begin":964,"end":1160},"obj":"Sentence"},{"id":"S8","span":{"begin":1161,"end":1285},"obj":"Sentence"},{"id":"S9","span":{"begin":1286,"end":1394},"obj":"Sentence"},{"id":"S10","span":{"begin":1395,"end":1632},"obj":"Sentence"},{"id":"S11","span":{"begin":1633,"end":1872},"obj":"Sentence"}],"text":"Inhibition of IL-4-inducible gene expression in human monocytes by type I and type II interferons.\nThe Th2-type cytokines, interleukin-4 (IL-4) and interleukin-13 (IL-13), induce expression of a distinct subset of genes in human monocytes, including FcepsilonRIIb (CD23), 15-lipoxygenase, IL-1 receptor antagonist (IL-1ra), and type I and type II IL-1 receptors (IL-1R). Type I interferons (IFN-alpha and IFN-beta) and type II interferon (IFN-gamma) inhibit induction of these genes by IL-4 and IL-13. However, the mechanism by which IFNs mediate this inhibition has not been defined. In this overview, we discuss the role of the transcription factor, STAT6 (signal transducer and activator of transcription-6) in mediating IL-4- and IL-13-induced gene expression in monocytes. We also discuss our recent findings that type I and type II IFNs suppress IL-4/IL-13-inducible gene expression by inhibiting tyrosine phosphorylation and nuclear translocation of STAT6. The ability of type I and type II IFNs to inhibit IL-4/IL-13-induced STAT6 activity is dose- and time-dependent, and is not unique to monocytes because IFNs induce the same effects in fibroblasts. Inhibition of STAT6 activity is not evident unless cells are preincubated with IFN for at least 1 h before IL-4 stimulation. Furthermore, inhibition can be blocked by actinomycin D, indicating a requirement for de novo transcription. We propose a model in which stimulation of monocytes by IFN activates de novo synthesis of an inhibitory factor, possibly one or more members of the SOCS/ SSI/CIS gene family, capable of suppressing activation of STAT6 by IL-4 and IL-13. Because STAT6 activation plays an essential role in IL-4/IL-13-induced gene expression, the ability of IFN-beta and IFN-gamma to inhibit STAT6 activity provides an explanation for how IFNs can suppress IL-4/IL-13-inducible gene expression."}
GENIAcorpus
{"project":"GENIAcorpus","denotations":[{"id":"T1","span":{"begin":14,"end":18},"obj":"protein_molecule"},{"id":"T2","span":{"begin":48,"end":63},"obj":"cell_type"},{"id":"T3","span":{"begin":103,"end":121},"obj":"protein_family_or_group"},{"id":"T4","span":{"begin":123,"end":136},"obj":"protein_molecule"},{"id":"T5","span":{"begin":138,"end":142},"obj":"protein_molecule"},{"id":"T6","span":{"begin":148,"end":162},"obj":"protein_molecule"},{"id":"T7","span":{"begin":164,"end":169},"obj":"protein_molecule"},{"id":"T8","span":{"begin":223,"end":238},"obj":"cell_type"},{"id":"T9","span":{"begin":250,"end":263},"obj":"protein_molecule"},{"id":"T10","span":{"begin":265,"end":269},"obj":"protein_molecule"},{"id":"T11","span":{"begin":272,"end":287},"obj":"protein_molecule"},{"id":"T12","span":{"begin":289,"end":313},"obj":"protein_molecule"},{"id":"T13","span":{"begin":315,"end":321},"obj":"protein_molecule"},{"id":"T14","span":{"begin":363,"end":368},"obj":"protein_family_or_group"},{"id":"T15","span":{"begin":371,"end":389},"obj":"protein_family_or_group"},{"id":"T16","span":{"begin":391,"end":400},"obj":"protein_molecule"},{"id":"T17","span":{"begin":405,"end":413},"obj":"protein_molecule"},{"id":"T18","span":{"begin":419,"end":437},"obj":"protein_family_or_group"},{"id":"T19","span":{"begin":439,"end":448},"obj":"protein_molecule"},{"id":"T20","span":{"begin":486,"end":490},"obj":"protein_molecule"},{"id":"T21","span":{"begin":495,"end":500},"obj":"protein_molecule"},{"id":"T22","span":{"begin":534,"end":538},"obj":"protein_family_or_group"},{"id":"T23","span":{"begin":630,"end":650},"obj":"protein_family_or_group"},{"id":"T24","span":{"begin":652,"end":657},"obj":"protein_molecule"},{"id":"T25","span":{"begin":659,"end":709},"obj":"protein_molecule"},{"id":"T26","span":{"begin":767,"end":776},"obj":"cell_type"},{"id":"T27","span":{"begin":852,"end":856},"obj":"protein_molecule"},{"id":"T28","span":{"begin":857,"end":862},"obj":"protein_molecule"},{"id":"T29","span":{"begin":903,"end":911},"obj":"amino_acid_monomer"},{"id":"T30","span":{"begin":932,"end":953},"obj":"other_name"},{"id":"T31","span":{"begin":957,"end":962},"obj":"protein_molecule"},{"id":"T32","span":{"begin":1014,"end":1018},"obj":"protein_molecule"},{"id":"T33","span":{"begin":1019,"end":1024},"obj":"protein_molecule"},{"id":"T34","span":{"begin":1033,"end":1038},"obj":"protein_molecule"},{"id":"T35","span":{"begin":1098,"end":1107},"obj":"cell_type"},{"id":"T36","span":{"begin":1116,"end":1120},"obj":"protein_family_or_group"},{"id":"T37","span":{"begin":1148,"end":1159},"obj":"cell_type"},{"id":"T38","span":{"begin":1175,"end":1180},"obj":"protein_molecule"},{"id":"T39","span":{"begin":1240,"end":1243},"obj":"protein_family_or_group"},{"id":"T40","span":{"begin":1268,"end":1272},"obj":"protein_molecule"},{"id":"T41","span":{"begin":1328,"end":1341},"obj":"other_organic_compound"},{"id":"T42","span":{"begin":1372,"end":1393},"obj":"other_name"},{"id":"T43","span":{"begin":1438,"end":1447},"obj":"cell_type"},{"id":"T44","span":{"begin":1451,"end":1454},"obj":"protein_family_or_group"},{"id":"T45","span":{"begin":1465,"end":1482},"obj":"other_name"},{"id":"T46","span":{"begin":1489,"end":1506},"obj":"protein_family_or_group"},{"id":"T47","span":{"begin":1544,"end":1569},"obj":"protein_family_or_group"},{"id":"T48","span":{"begin":1582,"end":1604},"obj":"other_name"},{"id":"T49","span":{"begin":1608,"end":1613},"obj":"protein_molecule"},{"id":"T50","span":{"begin":1617,"end":1621},"obj":"protein_molecule"},{"id":"T51","span":{"begin":1626,"end":1631},"obj":"protein_molecule"},{"id":"T52","span":{"begin":1641,"end":1646},"obj":"protein_molecule"},{"id":"T53","span":{"begin":1685,"end":1689},"obj":"protein_molecule"},{"id":"T54","span":{"begin":1690,"end":1695},"obj":"protein_molecule"},{"id":"T55","span":{"begin":1736,"end":1744},"obj":"protein_molecule"},{"id":"T56","span":{"begin":1749,"end":1758},"obj":"protein_molecule"},{"id":"T57","span":{"begin":1770,"end":1775},"obj":"protein_molecule"},{"id":"T58","span":{"begin":1817,"end":1821},"obj":"protein_family_or_group"},{"id":"T59","span":{"begin":1835,"end":1839},"obj":"protein_molecule"},{"id":"T60","span":{"begin":1840,"end":1845},"obj":"protein_molecule"}],"text":"Inhibition of IL-4-inducible gene expression in human monocytes by type I and type II interferons.\nThe Th2-type cytokines, interleukin-4 (IL-4) and interleukin-13 (IL-13), induce expression of a distinct subset of genes in human monocytes, including FcepsilonRIIb (CD23), 15-lipoxygenase, IL-1 receptor antagonist (IL-1ra), and type I and type II IL-1 receptors (IL-1R). Type I interferons (IFN-alpha and IFN-beta) and type II interferon (IFN-gamma) inhibit induction of these genes by IL-4 and IL-13. However, the mechanism by which IFNs mediate this inhibition has not been defined. In this overview, we discuss the role of the transcription factor, STAT6 (signal transducer and activator of transcription-6) in mediating IL-4- and IL-13-induced gene expression in monocytes. We also discuss our recent findings that type I and type II IFNs suppress IL-4/IL-13-inducible gene expression by inhibiting tyrosine phosphorylation and nuclear translocation of STAT6. The ability of type I and type II IFNs to inhibit IL-4/IL-13-induced STAT6 activity is dose- and time-dependent, and is not unique to monocytes because IFNs induce the same effects in fibroblasts. Inhibition of STAT6 activity is not evident unless cells are preincubated with IFN for at least 1 h before IL-4 stimulation. Furthermore, inhibition can be blocked by actinomycin D, indicating a requirement for de novo transcription. We propose a model in which stimulation of monocytes by IFN activates de novo synthesis of an inhibitory factor, possibly one or more members of the SOCS/ SSI/CIS gene family, capable of suppressing activation of STAT6 by IL-4 and IL-13. Because STAT6 activation plays an essential role in IL-4/IL-13-induced gene expression, the ability of IFN-beta and IFN-gamma to inhibit STAT6 activity provides an explanation for how IFNs can suppress IL-4/IL-13-inducible gene expression."}
metamap-sample
{"project":"metamap-sample","denotations":[{"id":"T1","span":{"begin":224,"end":229},"obj":"C0086418"},{"id":"T2","span":{"begin":49,"end":54},"obj":"C0086418"},{"id":"T3","span":{"begin":420,"end":438},"obj":"C0021745"},{"id":"T4","span":{"begin":79,"end":98},"obj":"C0021745"},{"id":"T5","span":{"begin":1439,"end":1448},"obj":"C0026473"},{"id":"T6","span":{"begin":1099,"end":1108},"obj":"C0026473"},{"id":"T7","span":{"begin":768,"end":777},"obj":"C0026473"},{"id":"T8","span":{"begin":230,"end":239},"obj":"C0026473"},{"id":"T9","span":{"begin":55,"end":64},"obj":"C0026473"},{"id":"T10","span":{"begin":1847,"end":1856},"obj":"C0669372"},{"id":"T11","span":{"begin":864,"end":873},"obj":"C0669372"},{"id":"T12","span":{"begin":20,"end":29},"obj":"C0669372"},{"id":"T13","span":{"begin":980,"end":986},"obj":"C0441729"},{"id":"T14","span":{"begin":820,"end":826},"obj":"C0441729"},{"id":"T15","span":{"begin":329,"end":335},"obj":"C0441729"},{"id":"T16","span":{"begin":68,"end":74},"obj":"C0441729"},{"id":"T17","span":{"begin":1300,"end":1310},"obj":"C1628982"},{"id":"T18","span":{"begin":1162,"end":1172},"obj":"C1628982"},{"id":"T19","span":{"begin":553,"end":563},"obj":"C1628982"},{"id":"T20","span":{"begin":1,"end":11},"obj":"C1628982"},{"id":"T21","span":{"begin":879,"end":889},"obj":"C0185117"},{"id":"T22","span":{"begin":754,"end":764},"obj":"C0185117"},{"id":"T23","span":{"begin":35,"end":45},"obj":"C0185117"},{"id":"T24","span":{"begin":1618,"end":1622},"obj":"C0021758"},{"id":"T25","span":{"begin":1269,"end":1272},"obj":"C0021758"},{"id":"T26","span":{"begin":725,"end":729},"obj":"C0021758"},{"id":"T27","span":{"begin":487,"end":491},"obj":"C0021758"},{"id":"T28","span":{"begin":124,"end":137},"obj":"C0021758"},{"id":"T29","span":{"begin":1627,"end":1632},"obj":"C0214743"},{"id":"T30","span":{"begin":1015,"end":1025},"obj":"C0214743"},{"id":"T31","span":{"begin":496,"end":501},"obj":"C0214743"},{"id":"T32","span":{"begin":149,"end":163},"obj":"C0214743"},{"id":"T33","span":{"begin":1737,"end":1745},"obj":"C0015980"},{"id":"T34","span":{"begin":406,"end":414},"obj":"C0015980"},{"id":"T35","span":{"begin":1763,"end":1770},"obj":"C0018790"},{"id":"T36","span":{"begin":1007,"end":1014},"obj":"C0018790"},{"id":"T37","span":{"begin":451,"end":458},"obj":"C0018790"},{"id":"T38","span":{"begin":273,"end":288},"obj":"C0003692"},{"id":"T39","span":{"begin":1609,"end":1614},"obj":"C1335877"},{"id":"T40","span":{"begin":1176,"end":1181},"obj":"C1335877"},{"id":"T41","span":{"begin":1034,"end":1038},"obj":"C1335877"},{"id":"T42","span":{"begin":958,"end":963},"obj":"C1335877"},{"id":"T43","span":{"begin":653,"end":658},"obj":"C1335877"},{"id":"T44","span":{"begin":1726,"end":1733},"obj":"C0085732"},{"id":"T45","span":{"begin":969,"end":976},"obj":"C0085732"},{"id":"T46","span":{"begin":1490,"end":1500},"obj":"C3463820"},{"id":"T47","span":{"begin":893,"end":903},"obj":"C3463820"},{"id":"T48","span":{"begin":348,"end":362},"obj":"C0063710"},{"id":"T49","span":{"begin":290,"end":294},"obj":"C0600251"},{"id":"T50","span":{"begin":372,"end":390},"obj":"C0021743"},{"id":"T51","span":{"begin":1260,"end":1261},"obj":"C0033727"},{"id":"T52","span":{"begin":1122,"end":1128},"obj":"C0205263"},{"id":"T53","span":{"begin":1026,"end":1033},"obj":"C0205263"},{"id":"T54","span":{"begin":741,"end":748},"obj":"C0205263"},{"id":"T55","span":{"begin":173,"end":178},"obj":"C0205263"},{"id":"T56","span":{"begin":1329,"end":1342},"obj":"C0010934"},{"id":"T57","span":{"begin":113,"end":122},"obj":"C0079189"},{"id":"T58","span":{"begin":1381,"end":1394},"obj":"C0040649"},{"id":"T59","span":{"begin":1545,"end":1549},"obj":"C0299250"},{"id":"T60","span":{"begin":1827,"end":1835},"obj":"C1260953"},{"id":"T61","span":{"begin":1583,"end":1593},"obj":"C1260953"},{"id":"T62","span":{"begin":844,"end":852},"obj":"C1260953"},{"id":"T63","span":{"begin":1194,"end":1196},"obj":"C1518422"},{"id":"T64","span":{"begin":1085,"end":1088},"obj":"C1518422"},{"id":"T65","span":{"begin":568,"end":571},"obj":"C1518422"},{"id":"T66","span":{"begin":1777,"end":1785},"obj":"C1561536"},{"id":"T67","span":{"begin":1182,"end":1190},"obj":"C1561536"},{"id":"T68","span":{"begin":1040,"end":1048},"obj":"C1561536"},{"id":"T69","span":{"begin":991,"end":998},"obj":"C0441730"},{"id":"T70","span":{"begin":831,"end":838},"obj":"C0441730"},{"id":"T71","span":{"begin":340,"end":347},"obj":"C0441730"},{"id":"T72","span":{"begin":715,"end":723},"obj":"C0086597"},{"id":"T73","span":{"begin":540,"end":547},"obj":"C0086597"},{"id":"T74","span":{"begin":667,"end":677},"obj":"C0040661"},{"id":"T75","span":{"begin":1149,"end":1160},"obj":"C0016030"},{"id":"T76","span":{"begin":1754,"end":1759},"obj":"C1552644"},{"id":"T77","span":{"begin":444,"end":449},"obj":"C1552644"},{"id":"T78","span":{"begin":1678,"end":1682},"obj":"C1705810"},{"id":"T79","span":{"begin":619,"end":623},"obj":"C1705810"},{"id":"T80","span":{"begin":1648,"end":1658},"obj":"C1879547"},{"id":"T81","span":{"begin":1595,"end":1605},"obj":"C1879547"},{"id":"T82","span":{"begin":1424,"end":1435},"obj":"C1292856"},{"id":"T83","span":{"begin":1274,"end":1285},"obj":"C1292856"},{"id":"T84","span":{"begin":1466,"end":1473},"obj":"C1515568"},{"id":"T85","span":{"begin":1373,"end":1380},"obj":"C1515568"},{"id":"T86","span":{"begin":1062,"end":1066},"obj":"C0040223"},{"id":"T87","span":{"begin":1474,"end":1483},"obj":"C0220781"},{"id":"T88","span":{"begin":1213,"end":1218},"obj":"C0007634"},{"id":"T89","span":{"begin":577,"end":584},"obj":"C1704788"},{"id":"T90","span":{"begin":1659,"end":1664},"obj":"C0600138"},{"id":"T91","span":{"begin":1052,"end":1056},"obj":"C0178602"},{"id":"T92","span":{"begin":241,"end":249},"obj":"C0332257"},{"id":"T93","span":{"begin":392,"end":401},"obj":"C1610033"},{"id":"T94","span":{"begin":1786,"end":1794},"obj":"C1999230"},{"id":"T95","span":{"begin":1456,"end":1465},"obj":"C1515877"},{"id":"T96","span":{"begin":594,"end":602},"obj":"C0814812"},{"id":"T97","span":{"begin":904,"end":928},"obj":"C1519726"},{"id":"T98","span":{"begin":1067,"end":1076},"obj":"C1701901"},{"id":"T99","span":{"begin":1518,"end":1521},"obj":"C0205447"},{"id":"T100","span":{"begin":660,"end":666},"obj":"C1710082"},{"id":"T101","span":{"begin":806,"end":814},"obj":"C2607943"},{"id":"T102","span":{"begin":933,"end":954},"obj":"C1518440"},{"id":"T103","span":{"begin":304,"end":314},"obj":"C0231491"},{"id":"T104","span":{"begin":1198,"end":1205},"obj":"C0332120"},{"id":"T105","span":{"begin":1318,"end":1325},"obj":"C0332206"},{"id":"T106","span":{"begin":1089,"end":1095},"obj":"C1710548"},{"id":"T107","span":{"begin":1138,"end":1145},"obj":"C1280500"},{"id":"T108","span":{"begin":1798,"end":1809},"obj":"C0681841"},{"id":"T109","span":{"begin":516,"end":525},"obj":"C0441712"},{"id":"T110","span":{"begin":1357,"end":1368},"obj":"C1514873"},{"id":"T111","span":{"begin":1409,"end":1414},"obj":"C3161035"},{"id":"T112","span":{"begin":1530,"end":1537},"obj":"C0680022"},{"id":"T113","span":{"begin":1668,"end":1677},"obj":"C0205224"},{"id":"T114","span":{"begin":1509,"end":1516},"obj":"C2362652"},{"id":"T115","span":{"begin":799,"end":805},"obj":"C0332185"},{"id":"T116","span":{"begin":1572,"end":1579},"obj":"C2698977"},{"id":"T117","span":{"begin":108,"end":112},"obj":"C0332307"},{"id":"T118","span":{"begin":295,"end":303},"obj":"C0597357"},{"id":"T119","span":{"begin":1252,"end":1257},"obj":"C0547044"},{"id":"T120","span":{"begin":1133,"end":1137},"obj":"C0445247"},{"id":"T121","span":{"begin":1501,"end":1507},"obj":"C1521761"},{"id":"T122","span":{"begin":205,"end":211},"obj":"C1515021"},{"id":"T123","span":{"begin":1555,"end":1558},"obj":"C1504308"},{"id":"T124","span":{"begin":1525,"end":1529},"obj":"C0205172"}],"text":"Inhibition of IL-4-inducible gene expression in human monocytes by type I and type II interferons.\nThe Th2-type cytokines, interleukin-4 (IL-4) and interleukin-13 (IL-13), induce expression of a distinct subset of genes in human monocytes, including FcepsilonRIIb (CD23), 15-lipoxygenase, IL-1 receptor antagonist (IL-1ra), and type I and type II IL-1 receptors (IL-1R). Type I interferons (IFN-alpha and IFN-beta) and type II interferon (IFN-gamma) inhibit induction of these genes by IL-4 and IL-13. However, the mechanism by which IFNs mediate this inhibition has not been defined. In this overview, we discuss the role of the transcription factor, STAT6 (signal transducer and activator of transcription-6) in mediating IL-4- and IL-13-induced gene expression in monocytes. We also discuss our recent findings that type I and type II IFNs suppress IL-4/IL-13-inducible gene expression by inhibiting tyrosine phosphorylation and nuclear translocation of STAT6. The ability of type I and type II IFNs to inhibit IL-4/IL-13-induced STAT6 activity is dose- and time-dependent, and is not unique to monocytes because IFNs induce the same effects in fibroblasts. Inhibition of STAT6 activity is not evident unless cells are preincubated with IFN for at least 1 h before IL-4 stimulation. Furthermore, inhibition can be blocked by actinomycin D, indicating a requirement for de novo transcription. We propose a model in which stimulation of monocytes by IFN activates de novo synthesis of an inhibitory factor, possibly one or more members of the SOCS/ SSI/CIS gene family, capable of suppressing activation of STAT6 by IL-4 and IL-13. Because STAT6 activation plays an essential role in IL-4/IL-13-induced gene expression, the ability of IFN-beta and IFN-gamma to inhibit STAT6 activity provides an explanation for how IFNs can suppress IL-4/IL-13-inducible gene expression."}