|
|
Anti-Inflammatory mechanisms of the proteinase-activated receptor 2-inhibiting peptide in human synovial cells
|
|
|
|
|
نویسنده
|
chen t.-l. ,lin y.-f. ,cheng c.-w. ,chen s.-y. ,sheu m.-t. ,leung t.-k. ,qin c.-h. ,chen c.-h.
|
منبع
|
journal of biomedical science - 2011 - دوره : 18 - شماره : 1
|
چکیده
|
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.
|
|
|
آدرس
|
department of anesthesiology,taipei medical university hospital,taipei, Taiwan, school of medical laboratory science and biotechnology,taipei medical university,taipei, Taiwan, graduate institute of clinical medicine,taipei medical university,taipei, Taiwan, school of medical laboratory science and biotechnology,taipei medical university,taipei, Taiwan, graduate institute of pharmaceutical sciences,taipei medical university,taipei, Taiwan, department of diagnostic radiology,taipei medical university hospital,taipei, Taiwan, school of medical laboratory science and biotechnology,taipei medical university,taipei, Taiwan, school of medical laboratory science and biotechnology,taipei medical university,taipei, Taiwan
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Authors
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|