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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2-3
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pubmed:dateCreated |
2000-11-7
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pubmed:abstractText |
Interleukin-10 (IL-10) has been used in the treatment of viral hepatitis in interferon-alpha (IFN-alpha) non-responders while patients who have high levels of IL-10 are poorly responsive to IFN-alpha. The mechanism underlying such controversial functions of IL-10 remains unknown. Here we demonstrated that injection of IL-10 into mice attenuated IFN-alpha-induced signal transducer and activator transcription factor (STAT)1 tyrosine phosphorylation in the liver. Reverse transcriptase-polymerase chain reaction assay demonstrated that mouse liver expressed high levels of IL-10 receptor 2 (IL-10R2) but low levels of IL-10R1. Injection of IL-10 into mice activated STAT3 but not STAT1 tyrosine phosphorylation and induced suppressor of cytokine signal 2 (SOCS2), SOCS3, and cytokine-inducible SH2 protein (CIS) mRNA expression in the liver. Furthermore, overexpression of SOCS2 or SOCS3 inhibited IFN-alpha-induced reporter activity in hepatic cells. These findings suggest that IL-10 inhibits IFN-alpha-activated STAT1 in the liver, at least in part, by inducing SOCS2, SOCS3, and CIS expression, which may be responsible for the resistance of IFN-alpha therapy in patients who have high levels of IL-10 and recommends that IL-10 treatment for viral hepatitis should be cautious.
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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 |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SOCS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/SOCS3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Socs2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Socs3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Stat1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Stat3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Suppressor of Cytokine Signaling...,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/cytokine inducible SH2-containing...
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0014-5793
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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 |
480
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
132-6
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11034314-Animals,
pubmed-meshheading:11034314-Cell Line,
pubmed-meshheading:11034314-Cytokines,
pubmed-meshheading:11034314-DNA-Binding Proteins,
pubmed-meshheading:11034314-Female,
pubmed-meshheading:11034314-Gene Expression,
pubmed-meshheading:11034314-Genes, Reporter,
pubmed-meshheading:11034314-Humans,
pubmed-meshheading:11034314-Immediate-Early Proteins,
pubmed-meshheading:11034314-Interferon-alpha,
pubmed-meshheading:11034314-Interleukin-10,
pubmed-meshheading:11034314-Liver,
pubmed-meshheading:11034314-Luciferases,
pubmed-meshheading:11034314-Mice,
pubmed-meshheading:11034314-Mice, Inbred ICR,
pubmed-meshheading:11034314-Phosphorylation,
pubmed-meshheading:11034314-Proteins,
pubmed-meshheading:11034314-RNA, Messenger,
pubmed-meshheading:11034314-Receptors, Interleukin,
pubmed-meshheading:11034314-Receptors, Interleukin-10,
pubmed-meshheading:11034314-Repressor Proteins,
pubmed-meshheading:11034314-STAT1 Transcription Factor,
pubmed-meshheading:11034314-STAT3 Transcription Factor,
pubmed-meshheading:11034314-Signal Transduction,
pubmed-meshheading:11034314-Spleen,
pubmed-meshheading:11034314-Suppressor of Cytokine Signaling Proteins,
pubmed-meshheading:11034314-Trans-Activators,
pubmed-meshheading:11034314-Transcription Factors,
pubmed-meshheading:11034314-Tyrosine,
pubmed-meshheading:11034314-src Homology Domains
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pubmed:year |
2000
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pubmed:articleTitle |
IL-10 attenuates IFN-alpha-activated STAT1 in the liver: involvement of SOCS2 and SOCS3.
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pubmed:affiliation |
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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