Triptolide inhibits CC chemokines expressed in rat adjuvant-induced arthritis.
Triptolide, a diterpenoid triepoxide from Tripterygium wilfordii Hook F (TWHF), has been proven to have potent immunosuppressive and anti-inflammatory activities. It has been clinically used to treat patients with rheumatoid arthritis (RA), in which chemokines play an important role in immune and inflammatory responses. To investigate the effect of triptolide on MCP-1, MIP-1alpha and RANTES, we used complete Freund's adjuvant to induce adjuvant-induced arthritis (AA) in rats. AA in rat is a useful experimental model of human RA. Our data show that the thickness of arthritic ankle decreases with administration of triptolide. Both mRNA and protein levels of MCP-1, MIP-1alpha and RANTES in synovial tissue of rats with AA are significantly higher than those in normal rats. mRNA levels of MIP-1alpha and RANTES increase in peripheral blood mononuclear cells of rats with AA in comparison with those in normal rats, whereas no MCP-1 mRNA can be detected. Triptolide can significantly inhibit rat AA induced over-expression of MCP-1, MIP-1alpha and RANTES at both mRNA and protein levels in a dose-dependent manner. These results may contribute to the therapeutic effects of triptolide in rheumatoid arthritis.
Wang
Yifan
Y
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, People's Republic of China. yfwang@sibs.ac.cn
Wei
Dengming
D
Lai
Zheng
Z
Le
Yanping
Y
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology*; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000276:immunology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors / Q000276:immunology; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007719:Knee Joint / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000037:antagonists & inhibitors / Q000276:immunology; D010616:Phenanthrenes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D019402:Macrophage Inflammatory Proteins; D010616:Phenanthrenes; D012333:RNA, Messenger; C001899:triptolide