TETRANDRINE INHIBITS SIGNAL-INDUCED NF-KAPPA-B ACTIVATION IN RAT ALVEOLAR MACROPHAGES

Tetrandrine is a bisbenzylisoquinoline alkaloid isolated from a natura l Chinese herbal medicine. While this alkaloid has been shown to exhib it antifibrotic and anti-inflammatory activities, its mechanism of act ion is unknown. The present study was designed to investigate the inhi bitory 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 i nhibit 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 the se 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 cytoplas mic inhibitor of the NF-kappa B transcription factor. (C) 1997 Academi c Press.