TY - JOUR
T1 - Anti-Inflammatory mechanisms of the proteinase-activated receptor 2-inhibiting peptide in human synovial cells
AU - Chen, Ta-Liang
AU - Lin, Yung-Feng
AU - Cheng, Chao-Wen
AU - Chen, Shi Yun
AU - Sheu, Ming-Thau
AU - Leung, Ting-Kai
AU - Qin, Cheng Hong
AU - Chen, Chien-Ho
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
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U2 - 10.1186/1423-0127-18-43
DO - 10.1186/1423-0127-18-43
M3 - Article
C2 - 21682866
AN - SCOPUS:79958845248
SN - 1021-7770
VL - 18
JO - Journal of Biomedical Science
JF - Journal of Biomedical Science
IS - 1
M1 - 43
ER -