Distinct expression of mast cell tryptase and protease activated receptor-2 in synovia of rheumatoid arthritis and osteoarthritis
Distinct expression of mast cell tryptase and protease activated receptor-2 in synovia of rheumatoid arthritis and osteoarthritis
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DOI：
10.1007/s10067-006-0495-8
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发表时间：
2007-08-01
影响因子：
3.4
通讯作者：
Yasui, Natsuo
中科院分区：
文献类型：
--
作者：
Nakano, Shunji;Mishiro, Takuya;Yasui, Natsuo
本研究的目的是研究肥大细胞类胰蛋白酶及其受体，蛋白酶激活受体-2（PAR-2），在类风湿关节炎（RA）和骨关节炎（OA）患者的滑膜和滑液中的差异表达。进行生化和免疫组化分析，以确定是否胰蛋白酶样蛋白酶在滑膜是相同的肥大细胞类胰蛋白酶。分别用[H-3]-胸苷掺入法和ELISA法检测肥大细胞类胰蛋白酶对滑膜成纤维细胞样细胞（SFCs）增殖和IL-8释放的影响。类胰蛋白酶样蛋白酶在类风湿关节炎患者的滑膜是相同的人肥大细胞类胰蛋白酶，这是由两个亚基：33和34 kDa。33-和34-kDa蛋白是31-kDa蛋白的不同糖基化形式，31-kDa蛋白是未糖基化的。类胰蛋白酶在RA滑液中的活性显著高于OA滑液，而在滑膜中的活性和表达相似。RA滑膜PAR-2 mRNA表达高于OA。肥大细胞类胰蛋白酶含有非糖基化的31 kDa亚基是滑液中的主要形式。RA患者的滑液中该亚单位的含量高于OA患者。肥大细胞类胰蛋白酶和PAR-2激活肽刺激SFCs增殖和IL-8的释放。肥大细胞类胰蛋白酶分泌到RA滑液中高于OA滑液。RA滑膜液中肥大细胞类胰蛋白酶通过PAR-2刺激SFCs增殖和促炎细胞因子的释放，可能是RA滑膜炎加重的原因之一。
The objective of this study is to examine the differential expression of mast cell tryptase and its receptor, protease-activated receptor-2 (PAR-2), in the synovium and synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Biochemical and immunohistochemical analyses were performed to determine whether the trypsin-like protease in the synovium is identical to mast cell tryptase. The effects of mast cell tryptase on the proliferation of synovial fibroblast-like cells (SFCs) and the release of IL-8 thereof were evaluated by the [H-3]-thymidine incorporation and ELISA, respectively. The trypsin-like protease in the synovium of RA patients was identical to human mast cell tryptase, which was composed of two subunits: 33 and 34 kDa. The 33- and 34-kDa proteins are different glycosylated forms of the 31-kDa protein, which was unglycosylated. Mast cell tryptase activity in RA synovial fluid was significantly higher than that in OA synovial fluid, while their activities and expression in the synovium were similar. Expression of PAR-2 mRNA in the synovium was higher in RA than in OA. Mast cell tryptase containing the unglycosylated 31-kDa subunit was the predominant form in synovial fluid. RA patients had higher amounts of this subunit in their synovial fluid than OA patients. Mast cell tryptase and PAR-2 activating peptide stimulated the proliferation of SFCs and release of IL-8 from these cells. Mast cell tryptase secretion into RA synovial fluid is higher than OA synovial fluid. Mast cell tryptase in synovial fluid stimulates the proliferation of SFCs and the release of pro-inflammatory cytokines via PAR-2, which may contribute to exacerbation of synovitis in RA.