The Effect Of IL-32γ On The Proliferation And Secretion Of Fibroblast-like Synoviocytes In Rheumatoid Arthritis

Rheumatoid arthritis(RA)is one of the most common systemic autoimmune diseases with high deformity, which is seriously harmful to the human health. It is pathologically characterized by synoviocytes"tumor-like"hyperplasia, inflammatory cell infiltration, angiogenesis and the progressive destruction of articular cartilage and bone. The pathogenesis of RA is very complex, it involves in the interaction between multiple cells, cell factors and signal pathways, although in the past dozens of years the pathology and physiology of RA was widely and deeply researched, it also made breakthrough progress, but the exact mechanism that contributes to disease pathogenesis are largely unknown. Therefore, it is necessary for us to further research and explore the pathogenesis of RA, and look for more new possible treatment targets.Interleukin-32 (IL-32) is a novel inflammatory cytokine,it has six or more major splice variants. It has been reported that IL-32 is highly expressed in RA synovial tissue biopsies, but it is not detected in the osteoarthritis synovial tissues. It promotes cell differentiation, affects cell apoptosis, and induces the expression of other proinflammatory cytokines and chemokines via multiple signal transduction pathways, it plays an important role in the inflammatory response, cardiovascular diseases and autoimmune diseases etc. IL-32γis the longest isoform, and it exhibited the highest biological activity. The role of IL-32γin the proliferation and secretion of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and regulation is explored by vitro experiments. It's discovered that the optimal concentration of IL-32γto the proliferation of RA-FLS was 100ng/ml by MTT. It's also discovered that IL-32γpromoted the proliferation of FLS through the NF-κB signaling pathways by cellular Immunohistochemistry. The influence of IL-32γto the cell cycle of RA-FLS was detected by flow cytometry assay (FCM), it's discovered that it incressed cell proliferation by promoting the transition of S to G2 phase. The expression levels of IL-6 in RA-FLS after stimulation with IL-32γwas detected by RT-PCR, the expression levels of IL-6 in RA-FLS which were pretreated with specific MAPK inhibitors (Erk1/2 inhibitor,PD98059;JNK inhibitor,SP600125;and p38 inhibitor,SB202190) for 30 min prior to the addition of IL-32γwas detected in the same way. The results manifested that IL-32γcould promote the expression levels of IL-6, while only in the pretreatment of FLS with Erk1/2 inhibitor (PD98059) , the expression levels of IL-6 was decreased, indicating that IL-32γpromotes the expression levels of IL-6 by the activation of Erk1/2.The work provides preparation for exploring the role of IL-32 in the inflammatory reaction process and its impossible mechanism, so as to provide theoretical foundation, experimental foundation and new possible targets for the treatment of RA.