NF-kappa B and transcriptional control of renal epithelial-inducible nitric oxide synthase.
Expression of the inducible isoform of nitric oxide synthase (iNOS) is subject to strict tissue specific transcriptional control. Recently, the NF-kappa B/Rel family of transcription factors, and particularly c-rel, was shown to mediate bacterial lipopolysaccharide (LPS) induction of iNOS in macrophages. Since LPS is only a weak inducer of iNOS in most nonimmune cells, we investigated the role of NF-kappa B in the regulation of iNOS expression in mouse renal epithelial cells. We report that LPS activates NF-kappa B in renal epithelium, but that this is not sufficient for induction of iNOS activity. The NF-kappa B complexes activated by LPS in renal epithelium differ from those in macrophages in that they lack c-rel, which may explain the absence of iNOS induction in renal epithelium. Conversely, LPS and interferon-gamma (IFN) synergize to induce renal epithelial iNOS. Functional iNOS promoter analysis indicate that this synergistic induction requires NF-kappa B. We conclude that NF-kappa B is necessary but not sufficient for the induction of renal epithelial iNOS expression, and that in contrast to macrophages, c-rel does not appear to play a major role in the regulation of renal epithelial iNOS.
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004848:Epithelium / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D007372:Interferons / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D014158:Transcription, Genetic
D008070:Lipopolysaccharides; D016328:NF-kappa B; D007372:Interferons; D019001:Nitric Oxide Synthase