Document Detail


Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis.
MedLine Citation:
PMID:  7569976     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glucocorticoids are among the most potent anti-inflammatory and immunosuppressive agents. They inhibit synthesis of almost all known cytokines and of several cell surface molecules required for immune function, but the mechanism underlying this activity has been unclear. Here it is shown that glucocorticoids are potent inhibitors of nuclear factor kappa B (NF-kappa B) activation in mice and cultured cells. This inhibition is mediated by induction of the I kappa B alpha inhibitory protein, which traps activated NF-kappa B in inactive cytoplasmic complexes. Because NF-kappa B activates many immunoregulatory genes in response to pro-inflammatory stimuli, the inhibition of its activity can be a major component of the anti-inflammatory activity of glucocorticoids.
Authors:
N Auphan; J A DiDonato; C Rosette; A Helmberg; M Karin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  270     ISSN:  0036-8075     ISO Abbreviation:  Science     Publication Date:  1995 Oct 
Date Detail:
Created Date:  1995-11-13     Completed Date:  1995-11-13     Revised Date:  2007-03-19    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  286-90     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla 92093-0636, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents / pharmacology*
Cell Line
Cell Nucleus / metabolism
Cytoplasm / metabolism
DNA-Binding Proteins / biosynthesis*
Dexamethasone / pharmacology*
Humans
Hybridomas
I-kappa B Proteins*
Immunosuppression*
Interleukin-2 / pharmacology
Lymph Nodes / drug effects,  metabolism
Mice
NF-kappa B / antagonists & inhibitors*,  metabolism
Receptors, Glucocorticoid / metabolism
T-Lymphocytes / drug effects,  metabolism*
Tetradecanoylphorbol Acetate / pharmacology
Transcription Factor AP-1 / metabolism
Transcription Factor RelA
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/DNA-Binding Proteins; 0/I-kappa B Proteins; 0/Interleukin-2; 0/NF-kappa B; 0/Receptors, Glucocorticoid; 0/Transcription Factor AP-1; 0/Transcription Factor RelA; 139874-52-5/NF-kappaB inhibitor alpha; 16561-29-8/Tetradecanoylphorbol Acetate; 50-02-2/Dexamethasone
Comments/Corrections
Comment In:
Science. 1995 Oct 13;270(5234):232-3   [PMID:  7569969 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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