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) inductio n 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 re gulation of iNOS expression in mouse renal epithelial cells. We report that LPS activates NF-kappa B in renal epithelium, but that this is n ot 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 induct ion in renal epithelium. Conversely, LPS and interferon-gamma (IFN) sy nergize to induce renal epithelial iNOS. Functional iNOS promoter anal ysis indicate that this synergistic induction requires NF-kappa B. We conclude that NF-kappa B is necessary but not sufficient for the induc tion of renal epithelial iNOS expression, and that in contrast to macr ophages, c-rel does not appear to play a major role in the regulation of renal epithelial iNOS.