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Enhancing Effect of IL-17 on IL-1-Induced IL-6 and Leukemia Inhibitory Factor Production by Rheumatoid Arthritis Synoviocytes and Its Regulation by Th2 Cytokines

Martine Chabaud, François Fossiez, Jean-Luc Taupin and Pierre Miossec
J Immunol July 1, 1998, 161 (1) 409-414;
Martine Chabaud
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François Fossiez
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Jean-Luc Taupin
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Pierre Miossec
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  • FIGURE 1.
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    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.
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    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.
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    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.
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    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

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    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

    ActivatorsnIL-6 Production (ng/ml)
    0+ IL-4+ IL-13+ IL-10
    069.8 ± 2.844.7 ± 6.3*+356b43.2 ± 12.4*+340b11.2 ± 1.6**+14b
    IL-14496.9 ± 55.1667.2 ± 67.9***+34682.8 ± 93.1***+37322.4 ± 61.8***−35
    IL-174282.7 ± 44.2357.8 ± 61.7***+27382.9 ± 55.6***+35179.2 ± 62.6***−37
    IL-1+ IL-174597.3 ± 57.8726.3 ± 39.9***+22798.7 ± 80.1***+34530.4 ± 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.

    • 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

    ActivatorsnLIF Production (ng/ml)
    0+ IL-4+ IL-13+ IL-10
    060.22 ± 0.030.09 ± 0.02*−59b0.05 ± 0.02*−77b0.21 ± 0.04−4b
    IL-141.66 ± 0.260.54 ± 0.09**−670.50 ± 0.08**−701.69 ± 0.02+2
    IL-1740.57 ± 0.060.19 ± 0.05*−670.13 ± 0.01*−770.53 ± 0.08−7
    IL-1+ IL-1741.92 ± 0.200.98 ± 0.07***−490.93 ± 0.14***−521.88 ± 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.

    • b Column represents % inhibition.

    • View popup
    Table III.

    Induction of IL-6 and LIF production by endogenous IL-17 produced by RA synovium piecesa

    ActivatorsIL-6 (ng/ml)LIF (ng/ml)
    Medium00.05 ± 0.01
    IL-1715.49 ± 2.410.98 ± 0.07
    IL-17 + mAb500.06 ± 0.01
    IL-17+ MX114.63 ± 3.8ND
    IL-1154.60 ± 13.481.64 ± 0.20
    IL-1 + mAb5145.95 ± 22.51.62 ± 0.18
    RA 54 supernatant151.3 ± 11.091.20 ± 0.04
    RA 54 supernatant + mAb552.7 ± 9.100.54 ± 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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The Journal of Immunology
Vol. 161, Issue 1
1 Jul 1998
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Enhancing Effect of IL-17 on IL-1-Induced IL-6 and Leukemia Inhibitory Factor Production by Rheumatoid Arthritis Synoviocytes and Its Regulation by Th2 Cytokines
Martine Chabaud, François Fossiez, Jean-Luc Taupin, Pierre Miossec
The Journal of Immunology July 1, 1998, 161 (1) 409-414;

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Enhancing Effect of IL-17 on IL-1-Induced IL-6 and Leukemia Inhibitory Factor Production by Rheumatoid Arthritis Synoviocytes and Its Regulation by Th2 Cytokines
Martine Chabaud, François Fossiez, Jean-Luc Taupin, Pierre Miossec
The Journal of Immunology July 1, 1998, 161 (1) 409-414;
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