Defective NF-kappaB signaling in dedifferentiated hepatoma cells.
Dedifferentiated rat hepatoma cells contain defects that result in the loss of hepatic gene expression, including the liver-enriched HNF4/HNF1alpha pathway. We examined induction of NF-kappaB, a key mediator of the inflammatory response, in hepatoma and dedifferentiated hepatoma cells. We show that exposure of dedifferentiated hepatoma cells, but not rat and human hepatoma cell lines, to proinflammatory cytokines or lipopolysaccharide resulted in rapid and sustained NF-kappaB induction. IkappaB-beta levels, but not NF-kappaB subunit p65 or IkappaB-alpha levels, were elevated compared with those for parental hepatoma cells. Interestingly, LPS-mediated activation of NF-kappaB was found to be independent of degradation of IkappaB-alpha or IkappaB-beta. Thus, these results suggest that loci responsible for maintaining hepatic gene expression also influence cellular responses to inflammatory agents.
St. Louis University Health Sciences Center, Pediatric Research Institute, St. Louis, Missouri, USA.
D M
DM
Kraus
G A
GA
Bulla
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D008070:Lipopolysaccharides / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D008115:Liver Regeneration; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017931:DNA Primers; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate