title: Tetrandrine inhibits signal-induced NF-kappa B activation in rat alveolar macrophages.
abstract: 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.
authors.affiliation: Department of Pathology, Pennsylvania State University College of Medicine, Hershey 17033, USA. fxc7@email.psu.edu/lmd4@email.psu.edu
authors.forename: F
authors.initials: F
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Sun
authors.forename: D C
authors.initials: DC
authors.lastname: Kuhn
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.forename: L J
authors.initials: LJ
authors.lastname: Gaydos
authors.forename: X
authors.initials: X
authors.lastname: Shi
authors.forename: L M
authors.initials: LM
authors.lastname: Demers
mesh_terms: 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
chemical_list: 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