Source:http://linkedlifedata.com/resource/pubmed/id/15240148
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2004-7-8
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| pubmed:abstractText |
Although the use of IFN-alpha in combination with ribavirin has improved the treatment efficacy of chronic hepatitis C virus (HCV) infection, 20-50% of patients still fail to eradicate the virus depending on the HCV genotype. Recently, overexpression of HCV core protein has been shown to inhibit IFN signaling and induce SOCS-3 expression. Aim of this study was to examine the putative role of SOCS proteins in IFN resistance. By Western blot analysis, a 4-fold induction of STAT-1/3 phosphorylation by IFN-alpha was observed in mock-transfected HepG2 clones. In contrast, IFN-induced STAT-1/3 phosphorylation was considerably downregulated by SOCS-1/3 overexpression. In mock-transfected cells, IFN-alpha induced 2',5'-OAS and myxovirus resistance A (MxA) promoter activity 40- to 80-fold and 10- to 35-fold, respectively, and this effect was abrogated in SOCS-1/3 overexpressing cells. As detected by Northern blot technique, IFN-alpha potently induced 2',5'-OAS and MxA mRNA expression in the control clones. Overexpression of SOCS-1 completely abolished both 2',5'-OAS and MxA mRNA expression, whereas SOCS-3 mainly inhibited 2',5'-OAS mRNA expression. Our results demonstrate that SOCS-1 and SOCS-3 proteins inhibit IFN-alpha-induced activation of the Jak-STAT pathway and expression of the antiviral proteins 2',5'-OAS and MxA. These data suggest a potential role of SOCS proteins in IFN resistance during antiviral treatment.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2',5'-Oligoadenylate Synthetase,
http://linkedlifedata.com/resource/pubmed/chemical/Antiviral Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SOCS1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/SOCS3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Suppressor of Cytokine Signaling...,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/myxovirus resistance proteins
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
0006-291X
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
30
|
| pubmed:volume |
320
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1007-14
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:15240148-2',5'-Oligoadenylate Synthetase,
pubmed-meshheading:15240148-Antiviral Agents,
pubmed-meshheading:15240148-Carcinoma, Hepatocellular,
pubmed-meshheading:15240148-Carrier Proteins,
pubmed-meshheading:15240148-Cell Line, Tumor,
pubmed-meshheading:15240148-GTP-Binding Proteins,
pubmed-meshheading:15240148-Humans,
pubmed-meshheading:15240148-Interferon-alpha,
pubmed-meshheading:15240148-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:15240148-Liver Neoplasms,
pubmed-meshheading:15240148-Repressor Proteins,
pubmed-meshheading:15240148-Suppressor of Cytokine Signaling Proteins,
pubmed-meshheading:15240148-Transcription Factors
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| pubmed:year |
2004
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| pubmed:articleTitle |
SOCS-1 and SOCS-3 inhibit IFN-alpha-induced expression of the antiviral proteins 2,5-OAS and MxA.
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| pubmed:affiliation |
Department of Internal Medicine II, Grosshadern, Klinikum der Ludwig, Maximilians-Universität, Munich 81377, Germany.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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