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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2003-4-22
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pubmed:abstractText |
Recent reports suggest that a novel mechanism of glucocorticoid (GC) immunosuppressive action is inhibition of signaling by IL-2 and IL-12, cytokines that use the Janus kinase-STAT signaling pathway. We investigated whether GCs could also block activation of Janus kinase-STAT signaling by IFN-gamma, a potent proinflammatory cytokine. Addition of dexamethasone to PBMC cultures resulted in a dramatic inhibition of IFN-gamma activation of STAT1. Several days of exposure to GCs were required for inhibition of IFN-gamma signaling to become apparent, and the underlying mechanism was down-regulation of STAT1 expression. GCs suppressed the expression of STAT1 mRNA, but did not affect STAT1 protein stability. STAT1 expression and IFN-gamma signaling were preferentially suppressed in macrophages. GCs did not act directly on macrophages, but worked indirectly by regulating macrophage-lymphocyte interactions that control STAT1 expression. GCs inhibited IFN-gamma-inducible gene expression, thus demonstrating the physiological significance of inhibition of signal transduction. Our results identify a novel level of regulation of IFN-gamma signaling, whereby GCs control the amplitude of IFN-gamma signaling by regulating STAT1 expression. These results suggest that inhibition of IFN-gamma signaling contributes to the immunosuppressive action of GCs.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD14,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL10,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CXC,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/IRF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Immunosuppressive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Milk Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/STAT5 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
170
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4833-9
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12707366-Anti-Inflammatory Agents,
pubmed-meshheading:12707366-Antigens, CD14,
pubmed-meshheading:12707366-Cells, Cultured,
pubmed-meshheading:12707366-Chemokine CXCL10,
pubmed-meshheading:12707366-Chemokines, CXC,
pubmed-meshheading:12707366-DNA-Binding Proteins,
pubmed-meshheading:12707366-Dexamethasone,
pubmed-meshheading:12707366-Down-Regulation,
pubmed-meshheading:12707366-Gene Expression Regulation,
pubmed-meshheading:12707366-Humans,
pubmed-meshheading:12707366-Immunosuppressive Agents,
pubmed-meshheading:12707366-Interferon Regulatory Factor-1,
pubmed-meshheading:12707366-Interferon-gamma,
pubmed-meshheading:12707366-Leukocytes, Mononuclear,
pubmed-meshheading:12707366-Milk Proteins,
pubmed-meshheading:12707366-Monocytes,
pubmed-meshheading:12707366-Phosphoproteins,
pubmed-meshheading:12707366-RNA, Messenger,
pubmed-meshheading:12707366-STAT1 Transcription Factor,
pubmed-meshheading:12707366-STAT5 Transcription Factor,
pubmed-meshheading:12707366-Signal Transduction,
pubmed-meshheading:12707366-Time Factors,
pubmed-meshheading:12707366-Trans-Activators
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pubmed:year |
2003
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pubmed:articleTitle |
Inhibition of IFN-gamma signaling by glucocorticoids.
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pubmed:affiliation |
Graduate Program in Immunology, Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10021, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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