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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 by RA bone explants. Bone samples from RA patients were incubated for 7 days in the presence of IL-17 (50 ng/ml) and/or IL-1 (100 pg/ml). (a) PICP levels (n = 3) in supernatants were measured by ELISA. Results are expressed as mean ± SEM of % induction of PICP production. Spontaneous production of PICP was 433 ± 133 ng/ml. (b) CTX levels in supernatants were measured by ELISA. Bone samples were incubated with IL-17 (n = 5), IL-1 (n = 5), and IL-17 + IL-1 (n = 2). Results are expressed as mean ± SEM. Spontaneous production of CTX was 104 ± 55 ng/ml. *P < 0.05 compared with control (medium alone).
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Figure 5: Effect of exogenous IL-17 on type I collagen metabolism by RA bone explants. Bone samples from RA patients were incubated for 7 days in the presence of IL-17 (50 ng/ml) and/or IL-1 (100 pg/ml). (a) PICP levels (n = 3) in supernatants were measured by ELISA. Results are expressed as mean ± SEM of % induction of PICP production. Spontaneous production of PICP was 433 ± 133 ng/ml. (b) CTX levels in supernatants were measured by ELISA. Bone samples were incubated with IL-17 (n = 5), IL-1 (n = 5), and IL-17 + IL-1 (n = 2). Results are expressed as mean ± SEM. Spontaneous production of CTX was 104 ± 55 ng/ml. *P < 0.05 compared with control (medium alone).

Mentions: First, we investigated the consequences of IL-17 on collagen synthesis by measuring the release of PICP by bone explants. The spontaneous production of PICP was 433 ± 133 ng/ml (range, 299–567 ng/ml). IL-17 inhibited such production by 42 ± 10% and IL-1 by 21 ± 3% (Fig. 5a).


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 by RA bone explants. Bone samples from RA patients were incubated for 7 days in the presence of IL-17 (50 ng/ml) and/or IL-1 (100 pg/ml). (a) PICP levels (n = 3) in supernatants were measured by ELISA. Results are expressed as mean ± SEM of % induction of PICP production. Spontaneous production of PICP was 433 ± 133 ng/ml. (b) CTX levels in supernatants were measured by ELISA. Bone samples were incubated with IL-17 (n = 5), IL-1 (n = 5), and IL-17 + IL-1 (n = 2). Results are expressed as mean ± SEM. Spontaneous production of CTX was 104 ± 55 ng/ml. *P < 0.05 compared with control (medium alone).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Effect of exogenous IL-17 on type I collagen metabolism by RA bone explants. Bone samples from RA patients were incubated for 7 days in the presence of IL-17 (50 ng/ml) and/or IL-1 (100 pg/ml). (a) PICP levels (n = 3) in supernatants were measured by ELISA. Results are expressed as mean ± SEM of % induction of PICP production. Spontaneous production of PICP was 433 ± 133 ng/ml. (b) CTX levels in supernatants were measured by ELISA. Bone samples were incubated with IL-17 (n = 5), IL-1 (n = 5), and IL-17 + IL-1 (n = 2). Results are expressed as mean ± SEM. Spontaneous production of CTX was 104 ± 55 ng/ml. *P < 0.05 compared with control (medium alone).
Mentions: First, we investigated the consequences of IL-17 on collagen synthesis by measuring the release of PICP by bone explants. The spontaneous production of PICP was 433 ± 133 ng/ml (range, 299–567 ng/ml). IL-17 inhibited such production by 42 ± 10% and IL-1 by 21 ± 3% (Fig. 5a).

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