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Kidney Int. 1995 Sep;48(3):674-82.

NF-kappa B and transcriptional control of renal epithelial-inducible nitric oxide synthase.

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Department of Pharmacology, University of Florida College of Medicine, Gainesville, USA.


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.

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