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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 mouse cartilage proteoglycan breakdown. Cartilage explants of patellae were pulse-labeled with 35S-sulfate for 3 h and incubated with IGF-1 (0.25 μg/ml), with or without IL-17 (10 or 100 ng/ml) and/or IL-1 (10 ng/ml) for 48 h. Cultures were performed with six patellae per variable, and data represent percentages of sulfate incorporation into proteoglycan ± SD relative to the values found with IGF-1 alone.
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Figure 3: Effect of exogenous IL-17 on mouse cartilage proteoglycan breakdown. Cartilage explants of patellae were pulse-labeled with 35S-sulfate for 3 h and incubated with IGF-1 (0.25 μg/ml), with or without IL-17 (10 or 100 ng/ml) and/or IL-1 (10 ng/ml) for 48 h. Cultures were performed with six patellae per variable, and data represent percentages of sulfate incorporation into proteoglycan ± SD relative to the values found with IGF-1 alone.

Mentions: Second, we looked at the effects of IL-17 and IL-1 on PG release. PG release during cartilage culture with cytokines was enhanced by 22% with 100 ng/ml IL-17, and by 25% with 10 ng/ml IL-1 (Fig. 3). Combination of IL-17 and IL-1 was more potent, increasing PG loss by 35%. Our results show that inhibition of PG synthesis by IL-17 was accompanied by PG breakdown, indicating that IL-17 induced cartilage degradation and suppression of its synthesis. These results combined also indicate a dual effect of IL-17 on cartilage, increasing PG breakdown and decreasing its synthesis.


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 mouse cartilage proteoglycan breakdown. Cartilage explants of patellae were pulse-labeled with 35S-sulfate for 3 h and incubated with IGF-1 (0.25 μg/ml), with or without IL-17 (10 or 100 ng/ml) and/or IL-1 (10 ng/ml) for 48 h. Cultures were performed with six patellae per variable, and data represent percentages of sulfate incorporation into proteoglycan ± SD relative to the values found with IGF-1 alone.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Effect of exogenous IL-17 on mouse cartilage proteoglycan breakdown. Cartilage explants of patellae were pulse-labeled with 35S-sulfate for 3 h and incubated with IGF-1 (0.25 μg/ml), with or without IL-17 (10 or 100 ng/ml) and/or IL-1 (10 ng/ml) for 48 h. Cultures were performed with six patellae per variable, and data represent percentages of sulfate incorporation into proteoglycan ± SD relative to the values found with IGF-1 alone.
Mentions: Second, we looked at the effects of IL-17 and IL-1 on PG release. PG release during cartilage culture with cytokines was enhanced by 22% with 100 ng/ml IL-17, and by 25% with 10 ng/ml IL-1 (Fig. 3). Combination of IL-17 and IL-1 was more potent, increasing PG loss by 35%. Our results show that inhibition of PG synthesis by IL-17 was accompanied by PG breakdown, indicating that IL-17 induced cartilage degradation and suppression of its synthesis. These results combined also indicate a dual effect of IL-17 on cartilage, increasing PG breakdown and decreasing its synthesis.

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