Tetrandrine inhibits signal-induced NF-kappa B activation in rat alveolar macrophages.
Tetrandrine is a bisbenzylisoquinoline alkaloid isolated from a natural Chinese herbal medicine. While this alkaloid has been shown to exhibit antifibrotic and anti-inflammatory activities, its mechanism of action is unknown. The present study was designed to investigate the inhibitory effect of tetrandrine on NF-kappa B activation in the alveolar macrophage. Three different provocative stimuli were used to activate NF-kappa B in these cells. The results indicate that tetrandrine can inhibit the activation of NF-kappa B and NF-kappa B-dependent reporter gene expression by LPS, PMA, and silica in a dose-dependent manner. In contrast, at the doses used, tetrandrine did not interfere with Sp-1 DNA binding activity or Sp-1-dependent reporter gene expression in these cells. Western blot analysis suggests that the inhibitory effect of tetrandrine on NF-kappa B activation can be attributed to its ability to suppress signal-induced degradation of I kappa B alpha, a cytoplasmic inhibitor of the NF-kappa B transcription factor.
Chen
F
F
Department of Pathology, Pennsylvania State University College of Medicine, Hershey 17033, USA. fxc7@email.psu.edu/lmd4@email.psu.edu
Sun
S
S
Kuhn
D C
DC
Lu
Y
Y
Gaydos
L J
LJ
Shi
X
X
Demers
L M
LM
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D044182:Benzylisoquinolines; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D017930:Genes, Reporter; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D012822:Silicon Dioxide / Q000494:pharmacology; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D044182:Benzylisoquinolines; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D016329:Sp1 Transcription Factor; D000072000:NF-KappaB Inhibitor alpha; C009438:tetrandrine; D012822:Silicon Dioxide; D004247:DNA; D013755:Tetradecanoylphorbol Acetate