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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 blockade of endogenous IL-17 on synovium and bone destruction. (a) Synovium (n = 5) and (b) bone explants (n = 3) from RA patients were incubated for 7 days with and without blocking anti-IL-17 mAb (10 μg/ml) or sIL-17R (1 μg/ml), which was added at the onset of the culture. CTX levels after 7 days of culture were measured by ELISA. Results are expressed as mean ± SEM of culture triplicates. Differences between IL-17 inhibitor treated groups and control groups were analyzed with the nonparametric Wilcoxon paired t test.*P < 0.05.
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Figure 6: Effect of blockade of endogenous IL-17 on synovium and bone destruction. (a) Synovium (n = 5) and (b) bone explants (n = 3) from RA patients were incubated for 7 days with and without blocking anti-IL-17 mAb (10 μg/ml) or sIL-17R (1 μg/ml), which was added at the onset of the culture. CTX levels after 7 days of culture were measured by ELISA. Results are expressed as mean ± SEM of culture triplicates. Differences between IL-17 inhibitor treated groups and control groups were analyzed with the nonparametric Wilcoxon paired t test.*P < 0.05.

Mentions: Regarding the two possible mechanisms of bone destruction in RA (ie diffusion of cytokines derived from synovium or production by juxta-articular bone), we looked at the contribution of endogenous IL-17 produced first by RA synovium and then by RA bone explants with specific IL-17 inhibitors. When RA synovium explants were incubated with sIL-17R or with an anti-IL-17 mAb (mAb5), spontaneous CTX production was inhibited in a same fashion by 75 and 88%, respectively (n = 5; Fig. 6a).


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 blockade of endogenous IL-17 on synovium and bone destruction. (a) Synovium (n = 5) and (b) bone explants (n = 3) from RA patients were incubated for 7 days with and without blocking anti-IL-17 mAb (10 μg/ml) or sIL-17R (1 μg/ml), which was added at the onset of the culture. CTX levels after 7 days of culture were measured by ELISA. Results are expressed as mean ± SEM of culture triplicates. Differences between IL-17 inhibitor treated groups and control groups were analyzed with the nonparametric Wilcoxon paired t test.*P < 0.05.
© Copyright Policy
Related In: Results  -  Collection

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Figure 6: Effect of blockade of endogenous IL-17 on synovium and bone destruction. (a) Synovium (n = 5) and (b) bone explants (n = 3) from RA patients were incubated for 7 days with and without blocking anti-IL-17 mAb (10 μg/ml) or sIL-17R (1 μg/ml), which was added at the onset of the culture. CTX levels after 7 days of culture were measured by ELISA. Results are expressed as mean ± SEM of culture triplicates. Differences between IL-17 inhibitor treated groups and control groups were analyzed with the nonparametric Wilcoxon paired t test.*P < 0.05.
Mentions: Regarding the two possible mechanisms of bone destruction in RA (ie diffusion of cytokines derived from synovium or production by juxta-articular bone), we looked at the contribution of endogenous IL-17 produced first by RA synovium and then by RA bone explants with specific IL-17 inhibitors. When RA synovium explants were incubated with sIL-17R or with an anti-IL-17 mAb (mAb5), spontaneous CTX production was inhibited in a same fashion by 75 and 88%, respectively (n = 5; Fig. 6a).

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