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IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis.

Chabaud M, Lubberts E, Joosten L, van Den Berg W, Miossec P - Arthritis Res. (2001)

Bottom Line: In human ex vivo models, addition of IL-17 enhanced IL-6 production and collagen destruction, and inhibited collagen synthesis by RA synovium explants.Addition of IL-1 in these conditions increased the effect of IL-17.In conclusion, the contribution of IL-17 derived from synovium and bone marrow T cells to joint destruction suggests the control of IL-17 for the treatment of RA.

View Article: PubMed Central - HTML - PubMed

Affiliation: INSERM U403, Faculté de Médecine Laennec, and Departments of Immunology and Rheumatology, Hôpital Edouard Herriot, Lyon, France.

ABSTRACT
The origin and role of IL-17, a T-cell derived cytokine, in cartilage and bone destruction during rheumatoid arthritis (RA) remain to be clarified. In human ex vivo models, addition of IL-17 enhanced IL-6 production and collagen destruction, and inhibited collagen synthesis by RA synovium explants. On mouse cartilage, IL-17 enhanced cartilage proteoglycan loss and inhibited its synthesis. On human RA bone explants, IL-17 also increased bone resorption and decreased formation. Addition of IL-1 in these conditions increased the effect of IL-17. Blocking of bone-derived endogenous IL-17 with specific inhibitors resulted in a protective inhibition of bone destruction. Conversely, intra-articular administration of IL-17 into a normal mouse joint induced cartilage degradation. In conclusion, the contribution of IL-17 derived from synovium and bone marrow T cells to joint destruction suggests the control of IL-17 for the treatment of RA.

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Effect of exogenous IL-17 on type I collagen metabolism in RA synovium explants. Synovium samples from RA patients were incubated for 7 days in the presence of IL-17 (50 ng/ml) or IL-1 (100 pg/ml). (a) PICP (n = 4) levels in supernatants were measured by ELISA. Results are expressed as mean ± SEM of % induction of PICP production. Spontaneous production of PICP was 371 ± 36 ng/ml. (b) CTX levels (n = 7) in supernatants were measured by ELISA. Results are expressed as mean ± SEM. Spontaneous production of CTX was 33 ± 11 ng/ml. *P < 0.05, **P < 0.01 compared with control (medium alone).
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Figure 2: Effect of exogenous IL-17 on type I collagen metabolism in RA synovium explants. Synovium samples from RA patients were incubated for 7 days in the presence of IL-17 (50 ng/ml) or IL-1 (100 pg/ml). (a) PICP (n = 4) levels in supernatants were measured by ELISA. Results are expressed as mean ± SEM of % induction of PICP production. Spontaneous production of PICP was 371 ± 36 ng/ml. (b) CTX levels (n = 7) in supernatants were measured by ELISA. Results are expressed as mean ± SEM. Spontaneous production of CTX was 33 ± 11 ng/ml. *P < 0.05, **P < 0.01 compared with control (medium alone).

Mentions: To investigate the consequences of addition of exogenous IL-17, we measured its effect on the destruction/formation activity of type I collagen by synovium explants. First, synthesis of type I collagen in synovium cultures was analyzed by measuring the release of PICP in supernatants by ELISA. Spontaneous production of PICP was 371 ± 36 ng/ml (range, 334–442 ng/ml). IL-17 inhibited these levels by a mean of 38% and inhibited IL-1 by a mean of 23% (n = 3; Fig. 2a).


IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis.

Chabaud M, Lubberts E, Joosten L, van Den Berg W, Miossec P - Arthritis Res. (2001)

Effect of exogenous IL-17 on type I collagen metabolism in RA synovium explants. Synovium samples from RA patients were incubated for 7 days in the presence of IL-17 (50 ng/ml) or IL-1 (100 pg/ml). (a) PICP (n = 4) levels in supernatants were measured by ELISA. Results are expressed as mean ± SEM of % induction of PICP production. Spontaneous production of PICP was 371 ± 36 ng/ml. (b) CTX levels (n = 7) in supernatants were measured by ELISA. Results are expressed as mean ± SEM. Spontaneous production of CTX was 33 ± 11 ng/ml. *P < 0.05, **P < 0.01 compared with control (medium alone).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC30709&req=5

Figure 2: Effect of exogenous IL-17 on type I collagen metabolism in RA synovium explants. Synovium samples from RA patients were incubated for 7 days in the presence of IL-17 (50 ng/ml) or IL-1 (100 pg/ml). (a) PICP (n = 4) levels in supernatants were measured by ELISA. Results are expressed as mean ± SEM of % induction of PICP production. Spontaneous production of PICP was 371 ± 36 ng/ml. (b) CTX levels (n = 7) in supernatants were measured by ELISA. Results are expressed as mean ± SEM. Spontaneous production of CTX was 33 ± 11 ng/ml. *P < 0.05, **P < 0.01 compared with control (medium alone).
Mentions: To investigate the consequences of addition of exogenous IL-17, we measured its effect on the destruction/formation activity of type I collagen by synovium explants. First, synthesis of type I collagen in synovium cultures was analyzed by measuring the release of PICP in supernatants by ELISA. Spontaneous production of PICP was 371 ± 36 ng/ml (range, 334–442 ng/ml). IL-17 inhibited these levels by a mean of 38% and inhibited IL-1 by a mean of 23% (n = 3; Fig. 2a).

Bottom Line: In human ex vivo models, addition of IL-17 enhanced IL-6 production and collagen destruction, and inhibited collagen synthesis by RA synovium explants.Addition of IL-1 in these conditions increased the effect of IL-17.In conclusion, the contribution of IL-17 derived from synovium and bone marrow T cells to joint destruction suggests the control of IL-17 for the treatment of RA.

View Article: PubMed Central - HTML - PubMed

Affiliation: INSERM U403, Faculté de Médecine Laennec, and Departments of Immunology and Rheumatology, Hôpital Edouard Herriot, Lyon, France.

ABSTRACT
The origin and role of IL-17, a T-cell derived cytokine, in cartilage and bone destruction during rheumatoid arthritis (RA) remain to be clarified. In human ex vivo models, addition of IL-17 enhanced IL-6 production and collagen destruction, and inhibited collagen synthesis by RA synovium explants. On mouse cartilage, IL-17 enhanced cartilage proteoglycan loss and inhibited its synthesis. On human RA bone explants, IL-17 also increased bone resorption and decreased formation. Addition of IL-1 in these conditions increased the effect of IL-17. Blocking of bone-derived endogenous IL-17 with specific inhibitors resulted in a protective inhibition of bone destruction. Conversely, intra-articular administration of IL-17 into a normal mouse joint induced cartilage degradation. In conclusion, the contribution of IL-17 derived from synovium and bone marrow T cells to joint destruction suggests the control of IL-17 for the treatment of RA.

Show MeSH
Related in: MedlinePlus