Innate immunity triggers IL-32 expression by fibroblast-like synoviooytes in rheumatoid arthritis

摘要

Interleukin-32 (IL-32) is a recently described cytokine, which is a strong inducer of proinflammatory cytokines such as TNF-alpha, IL-1beta, IL-6, IL-8. The expression of this cytokine is highly increased in rheumatoid synovial and correlated with the severity of joint inflammation. We therefore investigated the effect of innate immune stimulation by ligands of TLR2, TLR3, TLR4 and cytokines such as TNF-alpha and IFN-gamma, on IL-32 expression by fibroblast-like synoviocytes (FLS) RA. We have demonstrated that TLR2, TLR3 and TLR4 ligands as well as IFN-gamma and TNF-alpha induced IL-32 mRNA expression by RA FLS. IL-32 synthesis by resident cells of autoimmunity, is tightly regulated by innate immunity in rheumatoid arthritis. Thus, TNF-alpha, IFN-gamma, double-strand RNA, hyaluronic acid highly secreted in synovial tissues of RA patients, might trigger IL-32 secretion by FLS. IL-32 might therefore represent a relevant therapeutic target in RA.