Clarification of the pathophysiological significance of mast cell tryptase and protease activated receptor-2 (PAR-2) in articular destruction

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The purpose of this study is to clarify the pathophysiological significance of mast cell tryptase and protease activated receptor-2 (PAR-2) in articular lesions of patients with rheumatoid arthritis (RA).We obtained the following results.1.Trypsin-like activity in synovial fluid was significantly higher in RA than in osteoarthritis (OA) and healthy subjects, while in synovial tissue it was similar in RA and OA.2.The expression of PAR-2 mRNA in synovial tissue was higher in RA than in OA.3.The biochemical characteristics of trypsin-like enzyme purified from synovial tissue were similar to those of human mast cell tryptase.4.Human mast cell tryptase enhanced the proliferation of synovial fibroblast-like cells and the release of IL-8 from these cells.5.Furthermore, PAR-2 activating peptide stimulated the release of IL-8 from synovial fibroblast-like cells, suggesting that mast cell tryptase in synovial fluid stimulates the proliferation of synovial fibroblast-like cells and the release of IL-8 from these cells via activation of PAR-2.In summary, trypsin-like activity in synovial fluid was significantly higher in RA than in OA and healthy subjects. Mast cell tryptase and activation of its receptor (PAR-2) enhanced the proliferation of synovial fibroblast-like cells and the release of IL-8 from these cells. Thus, in rheumatoid lesions, mast cell tryptase is involved in amplifying arthritis via PAR-2.