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

Ta-Liang Chen, Yung-Feng Lin, Chao-Wen Cheng, Shi Yun Chen, Ming-Thau Sheu, Ting-Kai Leung, Cheng Hong Qin, Chien-Ho Chen

研究成果: 雜誌貢獻文章

4 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
文章編號43
期刊Journal of Biomedical Science
18
發行號1
DOIs
出版狀態已發佈 - 2011

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Pharmacology (medical)

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