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PMC:1064895 / 15484-21991 JSONTXT 23 Projects

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Id Subject Object Predicate Lexical cue
T115 0-7 Sentence denotes Results
T11220 9-96 Sentence denotes IL-17 production in PBMC from patients with RA, patients with OA and normal individuals
T116 9-96 Sentence denotes IL-17 production in PBMC from patients with RA, patients with OA and normal individuals
T11221 97-294 Sentence denotes PBMC were separated and cultured with PHA (5 μg/ml) from patients with RA, patients with OA, and age-matched normal controls; IL-17 levels were then determined in the culture supernatants (Fig. 1).
T117 97-294 Sentence denotes PBMC were separated and cultured with PHA (5 μg/ml) from patients with RA, patients with OA, and age-matched normal controls; IL-17 levels were then determined in the culture supernatants (Fig. 1).
T11222 295-634 Sentence denotes Although the amounts of basal IL-17 secretion were not different between RA, OA and normal controls (62 ± 31, 43 ± 19 and 43 ± 10 pg/ml, respectively), the IL-17 production stimulated by PHA was significantly higher in RA PBMC than in those from OA and controls (768 ± 295 versus 463 ± 211 pg/ml [P < 0.05] and 241 ± 29 pg/ml [P < 0.001]).
T118 295-634 Sentence denotes Although the amounts of basal IL-17 secretion were not different between RA, OA and normal controls (62 ± 31, 43 ± 19 and 43 ± 10 pg/ml, respectively), the IL-17 production stimulated by PHA was significantly higher in RA PBMC than in those from OA and controls (768 ± 295 versus 463 ± 211 pg/ml [P < 0.05] and 241 ± 29 pg/ml [P < 0.001]).
T11761 636-728 Sentence denotes Increased IL-17 production in PBMC of patients with RA by anti-CD3 and/or anti-CD28, and PHA
T119 636-728 Sentence denotes Increased IL-17 production in PBMC of patients with RA by anti-CD3 and/or anti-CD28, and PHA
T11762 729-1009 Sentence denotes Because IL-17 was already known from earlier reports to be produced mainly by activated T cells, we investigated the effect of different concentrations of anti-CD3 (1, 5 and 10 μg/ml) as a T cell activation, which showed a dose-dependent increase in IL-17 levels (data not shown).
T120 729-1009 Sentence denotes Because IL-17 was already known from earlier reports to be produced mainly by activated T cells, we investigated the effect of different concentrations of anti-CD3 (1, 5 and 10 μg/ml) as a T cell activation, which showed a dose-dependent increase in IL-17 levels (data not shown).
T11763 1010-1094 Sentence denotes On the basis of this, we chose 10 μg/ml as a stimulation concentration for anti-CD3.
T121 1010-1094 Sentence denotes On the basis of this, we chose 10 μg/ml as a stimulation concentration for anti-CD3.
T11764 1095-1299 Sentence denotes As shown in Table 1, anti-CD3 significantly upregulated IL-17 production up to 3.7-fold, and the combination of anti-CD28 and anti-CD3 produced more IL-17 (approximately 1.3-1.5-fold) than anti-CD3 alone.
T122 1095-1299 Sentence denotes As shown in Table 1, anti-CD3 significantly upregulated IL-17 production up to 3.7-fold, and the combination of anti-CD28 and anti-CD3 produced more IL-17 (approximately 1.3-1.5-fold) than anti-CD3 alone.
T11765 1300-1484 Sentence denotes Furthermore, when incubated with T cell mitogens such as PHA, increased IL-17 production was more pronounced than with anti-CD3 and anti-CD28 (588 ± 85 versus 211 ± 1 pg/ml; P < 0.05).
T123 1300-1484 Sentence denotes Furthermore, when incubated with T cell mitogens such as PHA, increased IL-17 production was more pronounced than with anti-CD3 and anti-CD28 (588 ± 85 versus 211 ± 1 pg/ml; P < 0.05).
T12597 1486-1568 Sentence denotes Regulation of IL-17 production in RA PBMC by inflammatory cytokines and chemokines
T124 1486-1568 Sentence denotes Regulation of IL-17 production in RA PBMC by inflammatory cytokines and chemokines
T12598 1569-1769 Sentence denotes Because RA PBMC include several cell types in addition to T cells, some inflammatory cytokines released from macrophages and other lymphocytes might have affected the production of IL-17 from T cells.
T125 1569-1769 Sentence denotes Because RA PBMC include several cell types in addition to T cells, some inflammatory cytokines released from macrophages and other lymphocytes might have affected the production of IL-17 from T cells.
T12599 1770-1926 Sentence denotes To evaluate the effects of inflammatory cytokines released by activated PBMC, we tested the effects of several cytokines and chemokines on IL-17 production.
T126 1770-1926 Sentence denotes To evaluate the effects of inflammatory cytokines released by activated PBMC, we tested the effects of several cytokines and chemokines on IL-17 production.
T12600 1927-2138 Sentence denotes We detected an increase in IL-17 level after stimulation with IL-15 (10 ng/ml), whereas with IL-1β (10 ng/ml), TNF-α (10 ng/ml), IL-18 (10 ng/ml) or TGF-β (10 ng/ml) the levels in IL-17 were unchanged (Fig. 2a).
T127 1927-2138 Sentence denotes We detected an increase in IL-17 level after stimulation with IL-15 (10 ng/ml), whereas with IL-1β (10 ng/ml), TNF-α (10 ng/ml), IL-18 (10 ng/ml) or TGF-β (10 ng/ml) the levels in IL-17 were unchanged (Fig. 2a).
T12601 2139-2417 Sentence denotes When treated with MCP-1 (10 ng/ml) or IL-6 (10 ng/ml), significant upregulations of IL-17 proteins were observed (62 ± 42 and 50 ± 10 versus 31 ± 11 pg/ml, respectively; P < 0.05), whereas none was observed with IL-8 (10 ng/ml), MIP-1α (10 ng/ml) or MIP-1β (10 ng/ml) (Fig. 2b).
T128 2139-2417 Sentence denotes When treated with MCP-1 (10 ng/ml) or IL-6 (10 ng/ml), significant upregulations of IL-17 proteins were observed (62 ± 42 and 50 ± 10 versus 31 ± 11 pg/ml, respectively; P < 0.05), whereas none was observed with IL-8 (10 ng/ml), MIP-1α (10 ng/ml) or MIP-1β (10 ng/ml) (Fig. 2b).
T13528 2419-2508 Sentence denotes Inhibition of IL-17 production by signal transduction inhibitors and anti-rheumatic drugs
T129 2419-2508 Sentence denotes Inhibition of IL-17 production by signal transduction inhibitors and anti-rheumatic drugs
T13529 2509-2642 Sentence denotes Having observed the increased IL-17 production in RA PBMC, it was important to know which signal transduction pathways were involved.
T130 2509-2642 Sentence denotes Having observed the increased IL-17 production in RA PBMC, it was important to know which signal transduction pathways were involved.
T13530 2643-2906 Sentence denotes As illustrated in Fig. 3, an significant decrease in anti-CD3-induced IL-17 production was observed when co-incubated with NF-κB inhibitor, PDTC and dexamethasone in comparison with anti-CD3 alone (38 ± 5 and 54 ± 11 versus 98 ± 19 pg/ml, respectively; P < 0.05).
T131 2643-2906 Sentence denotes As illustrated in Fig. 3, an significant decrease in anti-CD3-induced IL-17 production was observed when co-incubated with NF-κB inhibitor, PDTC and dexamethasone in comparison with anti-CD3 alone (38 ± 5 and 54 ± 11 versus 98 ± 19 pg/ml, respectively; P < 0.05).
T13531 2907-3115 Sentence denotes LY294002 and wortmannin, as an inhibitor of PI3K, also markedly inhibited the anti-CD3-induced IL-17 production in RA PBMC (98 ± 19 versus 38 ± 10 pg/ml [P < 0.005] and 48 ± 4 pg/ml [P < 0.05], respectively).
T132 2907-3115 Sentence denotes LY294002 and wortmannin, as an inhibitor of PI3K, also markedly inhibited the anti-CD3-induced IL-17 production in RA PBMC (98 ± 19 versus 38 ± 10 pg/ml [P < 0.005] and 48 ± 4 pg/ml [P < 0.05], respectively).
T13532 3116-3358 Sentence denotes The calcineurin inhibitors cyclosporin A and FK506 also downregulated the IL-17 secretion as well as the mitogen-activated protein kinase (MAPK) p38 inhibitor SB203580 did, whereas rapamycin and PD98059 had no effect on IL-17 levels (Fig. 3).
T133 3116-3358 Sentence denotes The calcineurin inhibitors cyclosporin A and FK506 also downregulated the IL-17 secretion as well as the mitogen-activated protein kinase (MAPK) p38 inhibitor SB203580 did, whereas rapamycin and PD98059 had no effect on IL-17 levels (Fig. 3).
T13533 3359-3548 Sentence denotes To evaluate the possibility of non-specific inhibition by the drug at high concentrations, we observed the dose response of PDTC and LY294002 for the inhibition of IL-17 production in PBMC.
T134 3359-3548 Sentence denotes To evaluate the possibility of non-specific inhibition by the drug at high concentrations, we observed the dose response of PDTC and LY294002 for the inhibition of IL-17 production in PBMC.
T13534 3549-3642 Sentence denotes There were dose-dependent inhibitions of IL-17 production with chemical inhibitors (Fig. 4a).
T135 3549-3642 Sentence denotes There were dose-dependent inhibitions of IL-17 production with chemical inhibitors (Fig. 4a).
T13535 3643-3735 Sentence denotes The other inhibitors in addition to PDTC and LY294002 showed the same pattern of inhibition.
T136 3643-3735 Sentence denotes The other inhibitors in addition to PDTC and LY294002 showed the same pattern of inhibition.
T13536 3736-3848 Sentence denotes Cytotoxic effects on PBMC by the chemical inhibitors at experimental concentrations were not observed (Fig. 4b).
T137 3736-3848 Sentence denotes Cytotoxic effects on PBMC by the chemical inhibitors at experimental concentrations were not observed (Fig. 4b).
T14487 3850-3882 Sentence denotes IL-17 mRNA expression in RA PBMC
T138 3850-3882 Sentence denotes IL-17 mRNA expression in RA PBMC
T14488 3883-4051 Sentence denotes To see whether enhanced IL-17 production could be regulated at a transcriptional level, semi-quantatitive reverse transcription–polymerase chain reaction was performed.
T139 3883-4051 Sentence denotes To see whether enhanced IL-17 production could be regulated at a transcriptional level, semi-quantatitive reverse transcription–polymerase chain reaction was performed.
T14489 4052-4240 Sentence denotes We observed a dose-dependent increase in IL-17 mRNA transcripts after stimulation with anti-CD3; this was inhibited by the PI3K inhibitor LY294002 and by the NF-κB inhibitor PDTC (Fig. 5).
T140 4052-4240 Sentence denotes We observed a dose-dependent increase in IL-17 mRNA transcripts after stimulation with anti-CD3; this was inhibited by the PI3K inhibitor LY294002 and by the NF-κB inhibitor PDTC (Fig. 5).
T14928 4242-4324 Sentence denotes Activation of PI3K/Akt signal transduction pathway on IL-17 production by anti-CD3
T141 4242-4324 Sentence denotes Activation of PI3K/Akt signal transduction pathway on IL-17 production by anti-CD3
T14929 4325-4444 Sentence denotes To determine downstream effector molecules of the PI3K pathway, we evaluated the activation of Akt by western blotting.
T142 4325-4444 Sentence denotes To determine downstream effector molecules of the PI3K pathway, we evaluated the activation of Akt by western blotting.
T14930 4445-4599 Sentence denotes As shown in Fig. 6, at 10 min of incubation with anti-CD3 (10 μg/ml) or LY294002 (20 μM), no difference in the amounts of phosphorylated Akt was observed.
T143 4445-4599 Sentence denotes As shown in Fig. 6, at 10 min of incubation with anti-CD3 (10 μg/ml) or LY294002 (20 μM), no difference in the amounts of phosphorylated Akt was observed.
T14931 4600-4775 Sentence denotes However, after 30 min of incubation, phosphorylated Akt increased (lane 2), and the effect of inhibition by LY294002 (lane 3) reached a peak at 60 min, lasting to 120–240 min.
T144 4600-4775 Sentence denotes However, after 30 min of incubation, phosphorylated Akt increased (lane 2), and the effect of inhibition by LY294002 (lane 3) reached a peak at 60 min, lasting to 120–240 min.
T14932 4776-4873 Sentence denotes In contrast, non-phosphorylated Akt and β-actin remained unchanged regardless of incubation time.
T145 4776-4873 Sentence denotes In contrast, non-phosphorylated Akt and β-actin remained unchanged regardless of incubation time.
T14933 4874-5071 Sentence denotes PHA, concanavalin A and IL-15 also demonstrated the same effect on phosphorylated Akt as shown with anti-CD3, which was an inhibition by wortmannin and PDTC as well as by LY294002 (data not shown).
T146 4874-5071 Sentence denotes PHA, concanavalin A and IL-15 also demonstrated the same effect on phosphorylated Akt as shown with anti-CD3, which was an inhibition by wortmannin and PDTC as well as by LY294002 (data not shown).
T15817 5073-5164 Sentence denotes Activation of the NF-κB and activator protein-1 (AP-1) pathway in the IL-17 promoter region
T147 5073-5164 Sentence denotes Activation of the NF-κB and activator protein-1 (AP-1) pathway in the IL-17 promoter region
T15818 5165-5453 Sentence denotes To investigate further the intracellular signaling pathway activated by anti-CD3 plus anti-CD28, concanavalin A, PHA and IL-15, and responsible for inducing IL-17 expression, we performed an electrophoretic mobility-shift assay (EMSA) of NF-κB recognition sites in the promoters of IL-17.
T148 5165-5453 Sentence denotes To investigate further the intracellular signaling pathway activated by anti-CD3 plus anti-CD28, concanavalin A, PHA and IL-15, and responsible for inducing IL-17 expression, we performed an electrophoretic mobility-shift assay (EMSA) of NF-κB recognition sites in the promoters of IL-17.
T15819 5454-5658 Sentence denotes As shown in Fig. 7a, nuclear extracts from RA PBMC stimulated with anti-CD3 plus anti-CD28 (lane 2) demonstrated increased binding of NF-κB to IL-17 promoters in comparison with that of controls (lane 1).
T149 5454-5658 Sentence denotes As shown in Fig. 7a, nuclear extracts from RA PBMC stimulated with anti-CD3 plus anti-CD28 (lane 2) demonstrated increased binding of NF-κB to IL-17 promoters in comparison with that of controls (lane 1).
T15820 5659-5758 Sentence denotes A supershift assay demonstrated shifted bands in p65 and p50 (lanes 3 and 4) not in c-Rel (lane 5).
T150 5659-5758 Sentence denotes A supershift assay demonstrated shifted bands in p65 and p50 (lanes 3 and 4) not in c-Rel (lane 5).
T15821 5759-5915 Sentence denotes In normal PBMC the same pattern was observed, but the degree of NF-κB activation by anti-CD3 plus anti-CD28 was less intense than that in RA PBMC (Fig. 7b).
T151 5759-5915 Sentence denotes In normal PBMC the same pattern was observed, but the degree of NF-κB activation by anti-CD3 plus anti-CD28 was less intense than that in RA PBMC (Fig. 7b).
T15822 5916-6071 Sentence denotes To confirm the link between PI3K activity and NF-κB, we performed EMSA to determine the NF-κB binding activity after treatment with both LY294002 and PDTC.
T152 5916-6071 Sentence denotes To confirm the link between PI3K activity and NF-κB, we performed EMSA to determine the NF-κB binding activity after treatment with both LY294002 and PDTC.
T15823 6072-6149 Sentence denotes Both agents block NF-κB DNA-binding activity in the IL-17 promoter (Fig. 7c).
T153 6072-6149 Sentence denotes Both agents block NF-κB DNA-binding activity in the IL-17 promoter (Fig. 7c).
T15824 6150-6267 Sentence denotes Western blotting for IκB-α showed inhibition of degradation of IκB-α by LY294002 and PDTC at the same time (Fig. 7c).
T154 6150-6267 Sentence denotes Western blotting for IκB-α showed inhibition of degradation of IκB-α by LY294002 and PDTC at the same time (Fig. 7c).
T15825 6268-6507 Sentence denotes In contrast, the AP-1 pathway was not activated by stimulation with anti-CD3 plus anti-CD28 (data not shown), demonstrating that NF-κB is the main intracellular signaling pathway in IL-17 production by activated PBMC from patients with RA.
T155 6268-6507 Sentence denotes In contrast, the AP-1 pathway was not activated by stimulation with anti-CD3 plus anti-CD28 (data not shown), demonstrating that NF-κB is the main intracellular signaling pathway in IL-17 production by activated PBMC from patients with RA.