Background Rheumatoid arthritis (RA) and osteoarthritis (OA) are chronic joint diseases in which fibroblast-like synoviocytes (FLS) actively participate in the synovitis- damage cycle, trough production of cytokines such as IL-6 and metalloproteinases (MMPs)(1). It has already been showed that serum IL-33 levels correlated with disease activity in RA(2). IL-33 is capable to enhance TNF-α effects in FLS(3). In the collagen-induced arthritis (CIA) model, the injection of IL-33 exacerbated the disease(4). Since ST2 receptor is expressed in FLS, it is hypothesized that IL-33 could activate FLS and increase downstream production of inflammatory cytokines.
Objectives To evaluate the production of IL-6, MMP-1, and MMP-3 by FLS stimulated with IL-33, TNF-α, and IL-1β.
Methods FLS were cultured from samples of synovial fluid and tissue of OA patients (OAFLS n=8), RA patients (RAFLS n=3), and patients without rheumatic disease (health) (HFLS n=4). FLS were stimulate with TNF-α at concentrations of 1; 5; 10 and 50 ng/ml, IL-1β at concentrations of 0.1; 0.2; 0.3; 0.5 and 1 ng/ml and IL-33 at concentrations of 1; 3; 10; 30; 100 ng/ml, soon after, IL-6, MMP-1, and MMP-3 levels were evaluated by ELISA, in the cell supernatant.
Results MMP-1, MMP-3 and IL-6 were constitutively expressed by FLS at baseline in all groups. Both TNF-α and IL-1β stimulated the production of IL-6 and MMP-1 with statistical significance in a dose-dependent manner in all three groups. Only IL-1β increased the production of MMP-3. TNF-α stimulated the production of MMP-3 only on HFLS. There was no difference between the concentration of MMP-1, MMP-3 and IL6 in the supernatant of OAFLS, ARFLS and HFLS when IL-33 stimulated and non-stimulated were compared.
Conclusions This study demonstrated that IL-33 failed to induce the production of IL-6, MMP-1 and MMP-3 by FLS of different diseases sources, suggesting that must be another cell type that plays the role of target to IL-33 in physiopathology of joint inflammation. The absence MMP-3 in response to TNF-α stimulus in RAFLS and OAFLS could be explain by saturation of this cytokine in synovial cells from these diseases.
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Acknowledgements Capes, Fapemig and Fundo de Apoio a Pesquisa e Ensino da Sociedade Brasileira de Reumatologia - FAPE-SBR.
Disclosure of Interest None declared
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