Modulatory Effect Of CCK-8 On Cell Proliferation And Secretion Of RSC-364 Cells Induced By RTNF-α And Its Signal Transduction Mechanisms

Major pathological changes of rheumatoid arthritis (RA) exist in joint, characterized by hyperplasia of synovium, infiltration of abundant inflammatory cells and progressive destruction of cartilage and bone structures, while vasculitis appears outside of joint. Three pathophysiological changes of synovium hyperplasia, inflammation and autoimmunity are comprehensively personificated in the whole process of RA, which interact, correlate and form a reticular network running through pathogenesis of RA. Fibroblast-like synoviocytes (FLSs) isolated from synovium of RA play a major role in the pathogenesis of rheumatoid arthritis (RA) by uncontrolled proliferation and secreting effector molecules, including cytokines, chemokines, prostaglandins (PGs) and proteolytic enzymes such as matrix metalloproteinases (MMPs), aggrecanase and cathepsin, which promote inflammation and joint destruction. TNF-αhas been reported to be one of the important inflammatory mediators. Alterations in proliferation and secretion of FLSs are known to play a pivotal role in the development of RA. Therefore, agents which have regulatory action on FLSs proliferation and secretion might act as the potent therapeutic drugs for RA, and searching for these agents has become the focus in the study field of RA. Cholecystokinin-octapeptide (CCK-8) is a kind of endogenous brain-gut peptide. Recent studies suggest the anti-inflammatory and immunomodulatory effect of CCK-8. It has been reported that CCK-8 could protect adult rats from joint inflammation induced by carrageenan. Our previous study demonstrated that CCK-8 could inhibit proliferation of rat fibroblast-like synoviocyte line RSC-364 cells and collagen-induced arthritis (CIA) FLSs, and could induce a decrease in MMP-2 and -9 secretion in RSC-364 cells induced by TNF-α, indicating that CCK-8 might have an...