Anti-Inflammatory mechanisms of the proteinase-activated receptor 2-inhibiting peptide in human synovial cells

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)-b 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-κb 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-κb 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. © 2011 chen et al; licensee biomed central ltd.