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IL-1 but not IL-18 induces osteoprotegerin and TRAIL in rheumatoid arthritis synovial fibroblasts


IL-18, a member of the IL-1 family, seems to be involved in bone destruction observed in rheumatoid arthritis (RA). Synovial proliferation secondary to an apoptosis defect and the RANK/RANKL system may be implicated in IL-18-induced bone destruction. Therefore, we examined IL-18, IL-1β and tumor necrosis factor (TNF)-α effects on RANKL, the pro-apoptic factor TRAIL, and osteoprotegerin (OPG), the soluble receptor of RANKL and TRAIL in synovial fibroblasts.

Materials and methods

Synovial fibroblasts (SFB) isolated from RA patients were stimulated with IL-18, IL-1β or TNF-α for 24 hours. Conditioned media was collected and mRNA was then extracted. Expression of OPG and soluble RANKL (RANKLs) were assessed by quantitative RT-PCR (Sybr Green) and by ELISA. IL-18, IL-1β and TNF-α did not induce RANKLs mRNA and protein expression. TRAIL expression was examined by semi-quantitative RT-PCR.


Unstimulated fibroblasts constitutively expressed OPG 2 ± 0.364 ng/ml. IL-18 did not increase mRNA and protein OPG expression. IL-1β induces OPG mRNA expression and a 14-fold increase of OPG protein (P < 0.05; n = 4). TNF-α also increases OPG mRNA and protein levels, but not significantly as compared with unstimulated RA SFBs (P = 0.21; n = 4). For TRAIL, IL-18 again does not induce TRAIL mRNA, whereas TNF-α-stimulated and IL-1β-stimulated synovial fibroblasts produce TRAIL mRNA.


IL-18 does not regulate the RANKL/OPG system and TRAIL in RA SFBs. IL-1β and TNF-α induce expression of OPG and TRAIL but not of RANKL. These results contrast with the known implication of these cytokines in bone destruction. Since OPG can also bind to TRAIL, a cytokine involved in apoptosis, OPG may block the pro-apoptotic function of TRAIL.

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Morel, J., Audo, R. & Combe, B. IL-1 but not IL-18 induces osteoprotegerin and TRAIL in rheumatoid arthritis synovial fibroblasts. Arthritis Res Ther 5 (Suppl 3), 66 (2003).

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