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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
32
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pubmed:dateCreated |
1992-12-16
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pubmed:abstractText |
Transforming growth factor (TGF)-beta and interleukin (IL)-10 inhibited lipopolysaccharide (LPS)-induced macrophage production of the inflammatory cytokines tumor necrosis factor-alpha (TNF), IL-1 alpha, and IL-1 beta by contrasting post-transcriptional mechanisms. TGF-beta acted slowly and late, as it required 12-16 h to exert a suppressive effect, and inhibited TNF production even when added 6 h after LPS. TGF-beta affected neither the level of TNF mRNA, the release of preformed TNF nor the degradation of TNF. Thus, TGF-beta appeared to inhibit translation of TNF mRNA. IL-10 not only suppressed TNF release to a 25-fold greater extent than TGF-beta, but also inhibited release of IL-1. In contrast to TGF-beta, IL-10 acted on an early step in cytokine production, its effect being maximal 3 h after addition of LPS. Unlike TGF-beta, IL-10 markedly suppressed TNF, IL-1 alpha, and IL-1 beta mRNA levels. However, this was accomplished without suppressing transcription of the corresponding genes. Moreover, cycloheximide antagonized the IL-10-dependent reduction in cytokine mRNA levels. Thus, IL-10 may induce a ribonuclease active on cytokine transcripts or may induce a protein that enhances the susceptibility of TNF, IL-1 alpha, and IL-1 beta mRNAs to ribonucleolytic action. We conclude that IL-10 and TGF-beta induce different phenotypes of macrophage deactivation, and deactivate macrophages by different mechanisms: IL-10 promotes degradation of cytokine mRNA, while TGF-beta primarily suppresses translation.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
267
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
23301-8
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:1429677-Animals,
pubmed-meshheading:1429677-Blotting, Northern,
pubmed-meshheading:1429677-Cells, Cultured,
pubmed-meshheading:1429677-Dose-Response Relationship, Drug,
pubmed-meshheading:1429677-Female,
pubmed-meshheading:1429677-Interleukin-1,
pubmed-meshheading:1429677-Interleukin-10,
pubmed-meshheading:1429677-Kinetics,
pubmed-meshheading:1429677-Lipopolysaccharides,
pubmed-meshheading:1429677-Macrophages,
pubmed-meshheading:1429677-Mice,
pubmed-meshheading:1429677-Mice, Inbred Strains,
pubmed-meshheading:1429677-RNA, Messenger,
pubmed-meshheading:1429677-Tetradecanoylphorbol Acetate,
pubmed-meshheading:1429677-Transforming Growth Factor beta,
pubmed-meshheading:1429677-Tumor Necrosis Factor-alpha
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pubmed:year |
1992
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pubmed:articleTitle |
Contrasting mechanisms for suppression of macrophage cytokine release by transforming growth factor-beta and interleukin-10.
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pubmed:affiliation |
Beatrice and Samuel A. Seaver Laboratory, Department of Medicine, Cornell University Medical College, New York, New York 10021.
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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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