Screening Out The Adhesion Inhibitor And Exploring On Its Adhesion Inhibitory Mechanisms

Rheumatoid arthritis (RA) is currently considered an autoimmune disease in which a pathological immune response attacks synovial cells, cartilage, and bone resulting in joint destruction and permanent disability. The infiltration of T cells, B cells, polymorphonuclear leukocytes, and microphages into synovial tissue, and production some inflammation mediators, such as IL-1, TNF-α etc, can stimulate the synovial cell proliferation and express some adhesion molecules, such as ICAM-1, VCAM-1 etc. The infiltration of polymorphonuclear leukocyte(PMN) and macrophages to the arthrosis cavities of patients with RA was associated with characteristic lesion for RA, and those infiltrated cells presented some count-receptor against synovial cell adhesion molecules , so we presumed that adhesion of PMN and synovial cell has a critical role in the pathogenesis of RA. Based on this presumed, we established a model of assaying the adhesion of PMNs to rats synovial cells(RSC), and screened two adhesion inhibitory agents, Oxyresveratrol(Mc-1) and Sanggenon C(Mc-2), from the extracted compounds of Chinese traditional medicine.Since lymphocytes infiltrated into synovial tissue and caused the inflammation of synovium is one of the crucial courses of RA, so if the compounds can suppress this course, it will be useful to treatment of the patients with RA. Based on this idea, we successfully cultured the human synovial cells(HSC), and researched the effects of Mc-1 and Mc-2 on HSC functions, such as adhesion to PMN and secretion of IL-8 in HSC, and the effects on the polymorphonuclear leukocytes(PMN) function, such as chemotaxis, respiration burst, production of NO, and production of TNF-α in C₅₇ mouse peritoneal macrophages, and also researched its anti-inflammatory effects in vivo. The result showed that the activation of HSC and PMN...