Expression of proteinase-activated receptors (PAR)-2 in articular chondrocytes is modulated by IL-1beta, TNF-alpha and TGF-beta.
Expression of proteinase-activated receptors (PAR)-2 in articular chondrocytes is modulated by IL-1beta, TNF-alpha and TGF-beta.
复制标题
DOI：
--
复制
发表时间：
2006
影响因子：
7
通讯作者：
Y. Xiang;K. Masuko-hongo;T. Sekine;H. Nakamura;K. Yudoh;K. Nishioka;T. Kato
中科院分区：
文献类型：
--
作者：
Y. Xiang;K. Masuko-hongo;T. Sekine;H. Nakamura;K. Yudoh;K. Nishioka;T. Kato
目的探讨炎性细胞因子对关节软骨细胞中蛋白水解酶激活受体-2(PAR-2)表达的调节作用。研究设计关节滑膜和软骨组织来自8例骨性关节炎(OA)患者和3例非关节病患者(“正常”)。用白介素1β、肿瘤坏死因子α或转化生长因子β1刺激软骨细胞。用逆转录聚合酶链式反应、Western blotting和免疫荧光法检测PAR-2的表达。定量聚合酶链式反应检测PAR-2信使核糖核酸的表达水平。结果PAR-2mRNA在骨性关节炎和正常软骨细胞及滑膜成纤维细胞中均有表达。而骨性关节炎软骨细胞中PAR-2的表达水平明显高于正常软骨细胞。长期培养显示，PAR-2mRNA在骨性关节炎中可持续表达至3代，而在正常软骨细胞中则不表达。IL-1β和TNF-α均上调正常和骨性关节炎软骨细胞PAR-2的表达。相反，转化生长因子-β1显著降低骨关节炎软骨细胞中PAR-2的表达，而增加正常软骨细胞中PAR-2的表达。结论促炎症细胞因子IL-1β和TNF-α上调了骨关节炎软骨细胞PAR-2的过度表达，而调节性细胞因子TGF-β1则下调了PAR-2的过度表达。PAR-2可能参与了骨关节炎的发病机制。
OBJECTIVE To investigate the modulation of expression of proteinase-activated receptor-2 (PAR-2) in articular chondrocytes by inflammatory cytokines. DESIGN Articular synovium and cartilage tissues were collected from eight patients with osteoarthritis (OA), and three patients without arthropathy ("normal"). Chondrocytes were stimulated with interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha or transforming growth factor (TGF)-beta1. The expression of PAR-2 was detected using reverse transcriptase-polymerase chain reaction (PCR), Western blotting and immunofluorescence. Quantitative PCR was performed to assess the expression levels of PAR-2 messenger RNA (mRNA). RESULTS The expression of PAR-2 mRNA was demonstrated in both OA and normal chondrocytes as well as in synovial fibroblasts. However, the level of PAR-2 in OA chondrocytes was much higher than in normal chondrocytes. Long-term culture revealed that PAR-2 mRNA expression was maintained up to three passages in OA but not in normal chondrocytes. IL-1beta and TNF-alpha both upregulated PAR-2 expression in normal and OA chondrocytes. In contrast, TGF-beta1 significantly decreased expression of PAR-2 in OA chondrocytes but increased PAR-2 in normal chondrocytes. CONCLUSIONS Overexpression of PAR-2 in OA chondrocytes is upregulated by proinflammatory cytokines IL-1beta and TNF-alpha, and down-regulated by regulatory cytokine TGF-beta1. PAR-2 may be involved in the pathogenesis of OA.