| Triptolide, a diterpenoid triepoxide from Tripterygium wilfordii Hook F (TWHF), has been proven to have potent immunosuppressive and anti-inflammatory activities in patients and animals with a variety of inflammatory and autoimmune diseases, including rheumatoid arthritis (RA). RA is characterized by synovial lining hyperplasia and chronic infiltration of inflammatory cells in synovial tissue. Various chemokines, such as MCP-1, MIP-1αand RANTES, interacting with their receptors on leucocytes are believed to play a pivotal role in the attraction of leukocytes to the site of inflammation and in the initiation and progression of the inflammatory process in RA.To investigate the effect of triptolide on MCP-1, MIP-1αand RANTES, we used complete Freund's adjuvant to induce adjuvant-induced arthritis (AIA) in rats. AIA in rat is a useful experimental model of human RA. Total RNA was extracted from synovial tissue and peripheral blood mononuclear cells (PBMC). The mRNA levels of MCP-1, MIP-1αand RANTES were assessed by semi-quantitative RT-PCR. Synovial tissue was immunostained with anti-MCP-1, anti-MIP-1αand anti-RANTES antibodies respectively to determine chemokines secretion in vivo. Our data show that the thickness of arthritic ankle decreases with administration of triptolide. Both mRNA and protein levels of MCP-1, MIP-1αand RANTES in synovial tissue of rats with AIA are significantly higher than those in normal rats. The mRNA levels of MIP-1αand RANTES increase in PBMC of rats with AIA in comparison with those in normal rats, whereas no MCP-1 mRNA can be detected. Triptolide can significantly inhibit rat AIA induced over-expression of MCP-1, MIP-1αand 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.
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