NDLI: Physical association and functional antagonism between the p65 subunit of transcription factor NF-kappa B and the glucocorticoid receptor.

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Physical association and functional antagonism between the p65 subunit of transcription factor NF-kappa B and the glucocorticoid receptor.

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Physical association and functional antagonism between the p65 subunit of transcription factor NF-kappa B and the glucocorticoid receptor.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ray, A. Prefontaine, K. E.
Description	Author Affiliation: Ray A ( Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520.);
Abstract	Glucocorticoids, which are widely used as antiinflammatory agents, downregulate the expression of the interleukin 6 gene and of additional cytokine genes involved in inflammatory responses. Conversely, the transcription factor NF-kappa B, a member of the Rel family of transcription factors, has been implicated in the induction of multiple genes involved in the early processes of immune and inflammatory responses. This prompted us to investigate whether one of the mechanisms by which glucocorticoids exert their antiinflammatory activities is through inhibition of gene activation mediated by NF-kappa B. We report that, in intact cells, activation of the interleukin 6 promoter by a combination of the factor NF-IL6 and the p65 subunit of NF-kappa B is inhibited by dexamethasone (ligand)-activated glucocorticoid receptor. Conversely, activation of the mouse mammary tumor virus promoter by a combination of dexamethasone and glucocorticoid receptor is inhibited by overexpression of p65. Furthermore, we provide evidence for physical association between glucocorticoid receptor and p65 in protein crosslinking and coimmunoprecipitation experiments, using either in vitro translated proteins or those present in cell extracts. These studies suggest that direct interactions between NF-kappa B and glucocorticoid receptor may partly account for the antiinflammatory properties of glucocorticoids in vivo.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	2
Volume Number	91
Language	English
Publisher	National Academy of Sciences
Publisher Date	1994-02-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	NF-kappa B Metabolism Receptors, Glucocorticoid Binding Sites CCAAT-Enhancer-Binding Proteins DNA, Complementary Genetics DNA-Binding Proteins Dexamethasone Pharmacology Gene Expression Regulation Drug Effects HeLa Cells Inflammation Etiology Interleukin-1 Interleukin-6 Molecular Sequence Data Antagonists & Inhibitors Chemistry Nuclear Proteins Promoter Regions, Genetic Protein Conformation Transcriptional Activation Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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