Dexamethasone suppresses iNOS gene expression by upregulating I-kappa B alpha and inhibiting NF-kappa B

The American Journal of Physiology
M E de VeraD A Geller

Abstract

Cytokine-stimulated inducible nitric oxide synthase (iNOS) gene expression is dependent on nuclear factor-kappa B (NF-kappa B) activation and is suppressed by glucocorticoids (GC). In this study we examined the molecular mechanisms of GC inhibition of iNOS expression in rat hepatocytes. Combinations of tumor necrosis factor-alpha, interleukin-1 beta, and interferon-gamma (cytokine mixture CM) induced high levels of iNOS mRNA and NO synthesis. The synthetic GC dexamethasone markedly repressed iNOS mRNA and protein expression, and nuclear run-on assays showed that this inhibition was occurring at the level of transcription. In addition, transfection studies showed that CM-stimulated activity of a 1.6-kb murine iNOS promoter fragment linked upstream of luciferase was suppressed by dexamethasone. Electromobility shift assays demonstrated that CM induced the appearance of an NF-kappa B complex composed of p50 and p65 subunits; the addition of dexamethasone markedly decreased this band shift. I-kappa B alpha expression was decreased by CM and upregulated in the presence of dexamethasone. Subsequently, nuclear p65 levels were decreased by dexamethasone compared with CM-treated cells. Thus GC repress NF-kappa B DNA-binding activity in ...Continue Reading

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Citations

Feb 9, 2000·American Journal of Physiology. Gastrointestinal and Liver Physiology·S L Freeman, W K MacNaughton
Mar 10, 2009·Annals of Biomedical Engineering·Mark ChenDean Ho
Nov 30, 2000·American Journal of Physiology. Renal Physiology·J SchwöbelM Mohaupt
Nov 25, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Maria Concetta MoraleBianca Marchetti
Oct 28, 2004·American Journal of Physiology. Renal Physiology·Zhiyuan YuBruce C Kone
Jul 15, 2004·American Journal of Physiology. Endocrinology and Metabolism·Anders H BergPhilipp E Scherer
Sep 19, 2006·World Journal of Gastroenterology : WJG·Halil EkenHuseyin Buyukbayram
Jun 3, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·L J GaliettaO Zegarra-Moran
May 8, 2000·Journal of Applied Toxicology : JAT·P Muriel
Jul 15, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Carol A GunnettDonald D Heistad
Apr 27, 2001·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·G R SwaroopsI R Whittle
Jan 29, 2021·Environmental Science and Pollution Research International·Eman E YassienHanaa S S Gazwi

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