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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 IL-6 production by RA synovium. Synovium samples from RA patients were incubated for 7 days in the presence of IL-17 (50 ng/ml; n = 10), IL-1 (100 pg/ml; n = 10), and IL-17 + IL-1 (n = 3). ELISA measured IL-6 levels in supernatants. Results are expressed as mean ± SEM of % induction of IL-6 production. Spontaneous production of IL-6 was 202 ± 57 ng/ml. *P < 0.01, **P < 0.05 compared with control (medium alone).
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Figure 1: Effect of exogenous IL-17 on IL-6 production by RA synovium. Synovium samples from RA patients were incubated for 7 days in the presence of IL-17 (50 ng/ml; n = 10), IL-1 (100 pg/ml; n = 10), and IL-17 + IL-1 (n = 3). ELISA measured IL-6 levels in supernatants. Results are expressed as mean ± SEM of % induction of IL-6 production. Spontaneous production of IL-6 was 202 ± 57 ng/ml. *P < 0.01, **P < 0.05 compared with control (medium alone).

Mentions: An ex vivo model of RA synovitis has been established using synovium pieces obtained at surgery [24]. Since RA synovium is composed of different cell types, we tested how IL-17, a T-cell product, would regulate the production of IL-6 and we compared its effect with that of IL-1. Thus synovium pieces were incubated with and without 50 ng/ml IL-17 and/or with and without 100 pg/ml IL-1. Levels of IL-6 were measured after 7 days of culture. IL-17 increased spontaneous IL-6 production (mean ± SEM, 202 ± 57 ng/ml) by 64 ± 17% (Fig. 1). IL-1 also increased spontaneous IL-6 production by 90 ± 27%. The combination of IL-17 and IL-1 induced a 189% increase of IL-6 production.


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 IL-6 production by RA synovium. Synovium samples from RA patients were incubated for 7 days in the presence of IL-17 (50 ng/ml; n = 10), IL-1 (100 pg/ml; n = 10), and IL-17 + IL-1 (n = 3). ELISA measured IL-6 levels in supernatants. Results are expressed as mean ± SEM of % induction of IL-6 production. Spontaneous production of IL-6 was 202 ± 57 ng/ml. *P < 0.01, **P < 0.05 compared with control (medium alone).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Effect of exogenous IL-17 on IL-6 production by RA synovium. Synovium samples from RA patients were incubated for 7 days in the presence of IL-17 (50 ng/ml; n = 10), IL-1 (100 pg/ml; n = 10), and IL-17 + IL-1 (n = 3). ELISA measured IL-6 levels in supernatants. Results are expressed as mean ± SEM of % induction of IL-6 production. Spontaneous production of IL-6 was 202 ± 57 ng/ml. *P < 0.01, **P < 0.05 compared with control (medium alone).
Mentions: An ex vivo model of RA synovitis has been established using synovium pieces obtained at surgery [24]. Since RA synovium is composed of different cell types, we tested how IL-17, a T-cell product, would regulate the production of IL-6 and we compared its effect with that of IL-1. Thus synovium pieces were incubated with and without 50 ng/ml IL-17 and/or with and without 100 pg/ml IL-1. Levels of IL-6 were measured after 7 days of culture. IL-17 increased spontaneous IL-6 production (mean ± SEM, 202 ± 57 ng/ml) by 64 ± 17% (Fig. 1). IL-1 also increased spontaneous IL-6 production by 90 ± 27%. The combination of IL-17 and IL-1 induced a 189% increase of IL-6 production.

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