[Triptolide inhibits vascular endothelial growth factor expression and production by endothelial cells].
OBJECTIVE
To investigate the effect of triptolide on vascular endothelial growth factor (VEGF) expression and secretion by endothelial cells, and explore the mechanism of anti-proteinuric effect of triptolide on glomerular nephritis.


METHODS
A human umbilical endothelium derived cell line (ECV-304) from American Type Culture Collection(ATCC) was used in this study. The effects of triptolide on VEGF mRNA expression, and intracellular protein production and secretion induced by PMA were measured by RT-PCR, flow cytometry and enzyme linked immunosorbent assay (ELISA). The effects of triptolide on endothelial c-jun/c-fos mRNA expression were investigated by RT-PCR.


RESULTS
100 ng/ml PMA significantly increased VEGF mRNA expression, intracellular production and secretion of VEGF in endothelial cells, while triptolide inhibited the effects of PMA in a dose-dependent manner. Moreover, triptolide dose-dependently inhibited endothelial c-jun/c-fos mRNA expression.


CONCLUSIONS
Triptolide is a potent inhibitor of VEGF expression and production, suggesting that the inhibitory influence of triptolide on VEGF expression and production may be one of the mechanisms underlying its anti-proteinuric effect on glomerular nephritis. Triptolide might inhibit VEGF expression and production by interfering with transcription factor AP-1 formation.
Hu
K
K
Nanjing University School of Medicine, Nanjing 210002, China.
Liu
Z
Z
Liu
D
D
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D004224:Diterpenes / Q000494:pharmacology*; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004852:Epoxy Compounds; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D010616:Phenanthrenes; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002273:Carcinogens; D004224:Diterpenes; D016228:Endothelial Growth Factors; D004852:Epoxy Compounds; D008222:Lymphokines; D010616:Phenanthrenes; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C001899:triptolide; D013755:Tetradecanoylphorbol Acetate