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

为探讨类风湿关节炎（RA）患者关节液中肥大细胞类胰蛋白酶和蛋白酶激活受体-2（PAR-2）活性的病理生理意义，本研究获得以下结果：1. RA患者关节液中类胰蛋白酶活性明显高于骨关节炎（OA）和健康人，RA和OA滑膜组织中PAR-2 mRNA的表达与RA相似。2. RA滑膜组织中PAR-2 mRNA的表达高于OA。人肥大细胞类胰蛋白酶能促进滑膜成纤维样细胞增殖和IL-2的释放，并能促进滑膜成纤维样细胞的增殖，5.此外，PAR-2激活肽刺激滑膜成纤维细胞样细胞释放IL-8，表明滑液中的肥大细胞类胰蛋白酶通过激活PAR-2刺激滑膜成纤维细胞样细胞增殖和从这些细胞释放IL-8。RA患者滑液中胰蛋白酶样活性显著高于OA和健康受试者。肥大细胞类胰蛋白酶及其受体（PAR-2）的激活增强了滑膜成纤维细胞样细胞的增殖和IL-8从这些细胞的释放。因此，在类风湿性病变中，肥大细胞类胰蛋白酶参与通过PAR-2放大关节炎。

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.