tailieunhanh - Báo cáo y học: "Anti-Inflammatory mechanisms of the proteinaseactivated receptor 2-inhibiting peptide in human synovial cells"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: Anti-Inflammatory mechanisms of the proteinaseactivated receptor 2-inhibiting peptide in human synovial cells | Chen et al. Journal of Biomedical Science 2011 18 43 http content 18 1 43 The cost of publication in Journal of Biomedical Science Is borne by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Anti-Inflammatory mechanisms of the proteinase-activated receptor 2-inhibiting peptide in human synovial cells Ta-Liang Chen1t Yung-Feng Lin2t Chao-Wen Cheng3 Shi-Yun Chen 2 Ming-Thau Sheu4 Ting-Kai Leung5 Cheng-Hong Qin2 and Chien-Ho Chen2 Abstract Background Osteoarthritis OA is a degenerative joint disease which affects the entire joint structure including the synovial membrane. Disease progression was shown to involve inflammatory changes mediated by proteinase-activated receptor PAR -2. Previous studies demonstrated that PAR-2 messenger m RNA and protein levels increased in OA synovial cells suggesting that PAR-2 is a potential therapeutic target of the disease. Methods We designed a PAR-2-inhibiting peptide PAR2-IP by changing an isoleucine residue in the PAR-2-activating peptide PAR2-AP SLIGKV to alanine generating the SLAGKV peptide. We used it to test PAR-2-mediated inflammatory responses including the expressions of cyclooxygenase COX -2 and matrix metalloproteinase MMP -1 and activation of nuclear factor NF -kB in human synovial cells. As a control expressions of COX-2 and MMP-1 were induced by trypsin at both the mRNA and protein levels. Results The PAR2-AP increased the expression of COX-2 more dramatically than that of MMP-1. When we treated cells with the designed PAR2-IP the trypsin-induced COX-2 level was completely inhibited at a moderate concentration of the PAR2-IP. With further examination of trypsin-induced NF-kB activation we observed sufficient inhibitory effects of the PAR2-IP in synoviosarcoma cells and primary synovial cells from OA patients. Conclusions Our study suggests that the PAR2-IP inhibits trypsin-induced NF-kB activation resulting in a reduction in inflammatory COX-2 expression