IL-6 INDUCED BY SPONDYLOARTHRITIS SYNOVIAL FLUIDS MODULATES METALLOPROTEINASE-9 ACTIVITY IN SYNOVIAL FIBROBLASTS

MARIA SILVIA DI GENARO; RODRIGO BLAS ; ALICIA MUNARRIZ ; RODOLFO PARDO-HIDALGO; HÉCTOR TAMASHIRO

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

SOCIEDADES DE BIOCIENCIAS

Spondyloarthritis (SpA) is the second most frequent chronic inflammatoryarthritis. Fibroblast-like synoviocytes (FLS) are involved inSpA pathogenesis. The cytokine IL-6 has emerged as an importanttherapeutic target for rheumatic disorders. However, the IL-6-mediatedmechanisms in chronic arthropathies are not fully understood.Metalloproteinase (MMP)-9 is associated with chronic inflammatorydiseases. In previous studies, we demonstrated that synovial fluids(SF) of SpA patients induce early IL-6 production by FLS. The IL-6blockade decreased MMP-9 activity of FLS. In the present work, weexplored the role of IL-6 induced by SpA SF in regulating MMP-9 activityin FLS. The SF of SpA patients were pooled (n=9). Primary FLSor SW982 cell line were stimulated with SpA SF pool at dilution 1:10in culture medium. The IL-6 function was blocked by the anti-IL-6receptor antagonist tocilizumab(TCZ) (200ug/ml). Because IL-6can activate JAK pathway, JAK-selective small molecule tofacitinib(1000 nM) was used to inhibit this pathway. The supernatants (SN)were collected after 48 h. The MMP-9 activity was determined by zymography.Cytokine levels in the SN were measured by ELISA. Wefound that in both primary FLS and SW982 cell line, TCZ decreasedsignificantly MMP-9 activity induced by SpA SF (p