Article Figures & Data
Figures
- FIGURE 1.
Effect of the combination of IL-1β and IL-17 on IL-6 production. A, Synoviocytes were cultured with increasing concentrations of IL-1β, measured in pg/ml, and IL-17, ng/ml, used alone and in combination. B, Synoviocytes were cultured with the combination of increasing concentrations ranging from 0 to 10 pg/ml of IL-1β and from 0 to 10 ng/ml of IL-17. IL-6 levels were measured by ELISA in day 7 supernatants.
- FIGURE 2.
Effect of the combination of IL-1β and IL-17 on LIF production. A, Synoviocytes were cultured with increasing concentrations of IL-1β, measured in pg/ml, and IL-17, ng/ml, used alone and in combination. B, Synoviocytes were cultured with the combination of increasing concentrations ranging from 0 to 10 pg/ml of IL-1β and from 0 to 10 ng/ml of IL-17. LIF levels were measured by ELISA in day 7 supernatants.
- FIGURE 3.
Effect of IL-4, IL-10, and IL-13 on the synergistic effect of IL-1β and IL-17 on IL-6 production. RA synoviocytes were cultured with suboptimal concentrations of IL-1β (1 pg/ml) with or without IL-17 (1 ng/ml) in the presence of 50 ng/ml of IL-4, IL-10, or IL-13. After 7 days of culture, IL-6 levels were measured by ELISA.
- FIGURE 4.
Effect of IL-4, IL-10, and IL-13 on the effect of IL-1β and IL-17 on LIF induction. RA synoviocytes were cultured with suboptimal concentrations of IL-1β (1 pg/ml) with or without IL-17 (5 ng/ml) in the presence of 50 ng/ml of IL-4, IL-10, or IL-13. After 7 days of culture, LIF levels were measured by ELISA.
Tables
- Table I.
Regulation by IL-4, IL-13, and IL-10 of IL-6 production by RA synoviocytes induced by IL-1β and IL-17a
Activators n IL-6 Production (ng/ml) 0 + IL-4 + IL-13 + IL-10 0 6 9.8 ± 2.8 44.7 ± 6.3* +356b 43.2 ± 12.4* +340b 11.2 ± 1.6** +14b IL-1 4 496.9 ± 55.1 667.2 ± 67.9*** +34 682.8 ± 93.1*** +37 322.4 ± 61.8*** −35 IL-17 4 282.7 ± 44.2 357.8 ± 61.7*** +27 382.9 ± 55.6*** +35 179.2 ± 62.6*** −37 IL-1+ IL-17 4 597.3 ± 57.8 726.3 ± 39.9*** +22 798.7 ± 80.1*** +34 530.4 ± 47.1*** −11 -
a 104 Synoviocytes were incubated in 96-well culture plates for 7 days with IL-1β (100 pg/ml) or IL-17 (20 ng/ml) or their combination in the presence of 50 ng/ml of IL-4, IL-10, or IL-13. After 7 days of culture, IL-6 levels were measured by ELISA and are expressed as the mean ± SEM of nseparate experiments. Differences in IL-6 production between the IL-4-, IL-13-, or IL-10-treated group and the control group were analyzed with the nonparametric Wilcoxon paired t test. *p < 0.005; **p < 0.01; ***p < 0.0001.
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b Column represents % induction.
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- Table II.
Regulation by IL-4, IL-3, and IL-10 of LIF production by RA synoviocytes induced by IL-1β and IL-17a
Activators n LIF Production (ng/ml) 0 + IL-4 + IL-13 + IL-10 0 6 0.22 ± 0.03 0.09 ± 0.02* −59b 0.05 ± 0.02* −77b 0.21 ± 0.04 −4b IL-1 4 1.66 ± 0.26 0.54 ± 0.09** −67 0.50 ± 0.08** −70 1.69 ± 0.02 +2 IL-17 4 0.57 ± 0.06 0.19 ± 0.05* −67 0.13 ± 0.01* −77 0.53 ± 0.08 −7 IL-1+ IL-17 4 1.92 ± 0.20 0.98 ± 0.07*** −49 0.93 ± 0.14*** −52 1.88 ± 0.31 −2 -
a RA synoviocytes were cultured as described in Table I⇑ in the presence of 50 ng/ml of IL-4, IL-10, or IL-13. After 7 days of culture, LIF levels were measured by ELISA and are expressed as the mean ± SEM for n separate experiments. Differences in LIF synthesis between IL-4-, IL-13-, or IL-10-treated groups and the control group were analyzed with the nonparametric Wilcoxon paired t test *p < 0.005; **p< 0.001; ***p < 0.05.
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b Column represents % inhibition.
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- Table III.
Induction of IL-6 and LIF production by endogenous IL-17 produced by RA synovium piecesa
Activators IL-6 (ng/ml) LIF (ng/ml) Medium 0 0.05 ± 0.01 IL-17 15.49 ± 2.41 0.98 ± 0.07 IL-17 + mAb5 0 0.06 ± 0.01 IL-17+ MX1 14.63 ± 3.8 ND IL-1 154.60 ± 13.48 1.64 ± 0.20 IL-1 + mAb5 145.95 ± 22.5 1.62 ± 0.18 RA 54 supernatant 151.3 ± 11.09 1.20 ± 0.04 RA 54 supernatant + mAb5 52.7 ± 9.10 0.54 ± 0.01 -
a Cytokines (IL-1β, 100 pg/ml, or IL-17, 50 ng/ml) or synovium piece supernatants were preincubated in the presence or absence of 1 μg/ml of a control mAb (MX1) or 1 μg/ml of anti-IL-17 (mAb5). The mixture was incubated with synoviocytes for 12 h. Plates were washed before addition of fresh medium. IL-6 and LIF levels were determined by ELISA in the 48-h supernatants.
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