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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 bone explants. Bone samples from RA patients were incubated for 7 days in the presence of IL-17 (50 ng/ml; n = 5), IL-1 (100 pg/ml; n = 5), and IL-17 + IL-1 (n = 2). 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 220 ± 95 ng/ml. *P < 0.05 compared with control (medium alone).
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Figure 4: Effect of exogenous IL-17 on IL-6 production by RA bone explants. Bone samples from RA patients were incubated for 7 days in the presence of IL-17 (50 ng/ml; n = 5), IL-1 (100 pg/ml; n = 5), and IL-17 + IL-1 (n = 2). 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 220 ± 95 ng/ml. *P < 0.05 compared with control (medium alone).

Mentions: Finally, the third target to consider was bone because RA leads to early juxta-articular bone loss. Regarding the origin of cytokines affecting bone, cytokines produced by synovium can reach bone by diffusion or be released by the bone microenvironment itself. IL-6 has been shown to favor osteoclastogenesis. An ex vivo model of bone resorption was established to investigate the effect of IL-17 on IL-6 release by bone using bone pieces obtained at the site of joint surgery of patients with RA as previously described [25]. Bone pieces were incubated, as for synovium pieces, with and without 50 ng/ml IL-17 and/or with and without 100 pg/ml IL-1. IL-17 increased the spontaneous production (220 ± 95 ng/ml) of IL-6 by these bone pieces by 41 ± 25% and that of IL-1 by 73 ± 21% (Fig. 4). The combination of IL-17 and IL-1 had a much larger effect on IL-6 production (171 ± 55%).


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 bone explants. Bone samples from RA patients were incubated for 7 days in the presence of IL-17 (50 ng/ml; n = 5), IL-1 (100 pg/ml; n = 5), and IL-17 + IL-1 (n = 2). 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 220 ± 95 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 4: Effect of exogenous IL-17 on IL-6 production by RA bone explants. Bone samples from RA patients were incubated for 7 days in the presence of IL-17 (50 ng/ml; n = 5), IL-1 (100 pg/ml; n = 5), and IL-17 + IL-1 (n = 2). 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 220 ± 95 ng/ml. *P < 0.05 compared with control (medium alone).
Mentions: Finally, the third target to consider was bone because RA leads to early juxta-articular bone loss. Regarding the origin of cytokines affecting bone, cytokines produced by synovium can reach bone by diffusion or be released by the bone microenvironment itself. IL-6 has been shown to favor osteoclastogenesis. An ex vivo model of bone resorption was established to investigate the effect of IL-17 on IL-6 release by bone using bone pieces obtained at the site of joint surgery of patients with RA as previously described [25]. Bone pieces were incubated, as for synovium pieces, with and without 50 ng/ml IL-17 and/or with and without 100 pg/ml IL-1. IL-17 increased the spontaneous production (220 ± 95 ng/ml) of IL-6 by these bone pieces by 41 ± 25% and that of IL-1 by 73 ± 21% (Fig. 4). The combination of IL-17 and IL-1 had a much larger effect on IL-6 production (171 ± 55%).

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