THROMBIN RECEPTOR-MEDIATED SYNOVIAL PROLIFERATION IN PATIENTS WITH RHEUMATOID-ARTHRITIS

Synovial cell proliferation is one of the pathological bases of rheuma toid arthritis (RA). Several cytokines including IL-1 and IL-6 and gro wth factors have been shown to be involved in the synovial cell prolif eration in RA, Thrombin is a multifunctional protease and acts as a mi togen for several cell types through its specific receptor. To assess whether thrombin is involved in overproliferation of rheumatoid synovi al cells, we measured the concentration of thrombin-antithrombin III ( ATIII) complex (TAT) in synovial fluid obtained from patients with RA or osteoarthritis (OA). We also examined the effect of thrombin or thr ombin receptor agonist peptide (TRAP) on cell growth of synovial cell clones (SCCs) established from an RA patient. The concentrations of TA T in the synovial fluid from patients with RA were significantly highe r than in those with OA. Moreover, both thrombin and TRAP enhanced pro liferation of synovial cells in vitro. We also characterized the expre ssion of thrombin receptor mRNA by reverse transcription-PCR. The expr ession of mRNA for thrombin receptor was up-regulated by thrombin or T RAP stimulation. Thrombin receptor antigen was also detected on both S CCs and synovial tissue from RA patients by immunostaining using a mon oclonal antibody against thrombin receptor. These findings indicate th at thrombin may act as a mitogen for synovial cells through thrombin r eceptor and may play some role in synovial overproliferation and remod eling in RA. (C) 1995 Academic Press, Inc.