%0 Journal Article %T Anti-Inflammatory mechanisms of the proteinase-activated receptor 2-inhibiting peptide in human synovial cells %A Ta-Liang Chen %A Yung-Feng Lin %A Chao-Wen Cheng %A Shi-Yun Chen %A Ming-Thau Sheu %A Ting-Kai Leung %A Cheng-Hong Qin %A Chien-Ho Chen %J Journal of Biomedical Science %D 2011 %I BioMed Central %R 10.1186/1423-0127-18-43 %X 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)-¦ÊB 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.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-¦ÊB activation, we observed sufficient inhibitory effects of the PAR2-IP in synoviosarcoma cells and primary synovial cells from OA patients.Our study suggests that the PAR2-IP inhibits trypsin-induced NF-¦ÊB activation, resulting in a reduction in inflammatory COX-2 expression in synovial cells. Application of PAR2-IP is suggested as a potential therapeutic strategy for OA.Osteoarthritis (OA) is a degenerative joint disease in which degradation of the cartilage structure is found. A recent investigation demonstrated the significant involvement of inflammatory processes in OA pathogenesis [1]. Induction of inflammatory factors, such as interleukin (IL)-1¦Â, by hormone disruption and/or other factors was shown to contribute to the disease progression [2,3].Studies on patients and a mouse model demonstrated a key role of proteinase-activated receptor (PAR)-2 in mediating arthritic inflammation [4-7]. PARs belong to the G-protein coupled receptor family that is activated by serine protease-mediated cleavage of the N-terminus of the receptors [8,9]. Mounting evidence indicated that trypsin cleaves PAR-2 at R34¡ýS35LIGKV (in human) to expose a hexameric-tethered peptide that binds to conserved regions in the extra %U http://www.jbiomedsci.com/content/18/1/43