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rdf:type |
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lifeskim:mentions |
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0024432,
umls-concept:C0079904,
umls-concept:C0085295,
umls-concept:C0086418,
umls-concept:C0205225,
umls-concept:C0301625,
umls-concept:C0332120,
umls-concept:C0441712,
umls-concept:C1120843,
umls-concept:C1314939,
umls-concept:C1554184,
umls-concept:C1819464
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pubmed:issue |
10
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pubmed:dateCreated |
2002-5-7
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pubmed:abstractText |
IL-10 is a potent anti-inflammatory cytokine and inhibitor of TNF-alpha production. The molecular pathways by which IL-10 inhibits TNF-alpha production are obscure, with diverse mechanisms having been published. In this study, a new approach has been taken for the study of human cells. Adenovirus was used to deliver TNF-alpha promoter-based luciferase reporter genes to primary human monocytic cells. The reporter genes were highly responsive to macrophage activation and appeared to mirror the behavior of the endogenous TNF-alpha gene. When added, either with or after the stimulus, IL-10 required the 3' untranslated region of the TNF-alpha gene to inhibit luciferase mRNA and protein expression, indicating a posttranscriptional mechanism. However, if macrophages were incubated with IL-10 before activation, inhibition of gene expression was also mediated by the 5' promoter, suggesting a transcriptional mechanism. To our knowledge, this is the first time that a dual mechanism for IL-10 function has been demonstrated. Studies to elucidate the mechanisms underlying the inhibition of TNF-alpha production addressed the effect of IL-10 on the activation of p38 mitogen-activated protein kinase and NF-kappaB. However, these studies could demonstrate no requirement for the inhibition of p38 mitogen-activated protein kinase or NF-kappaB activation as potential mechanisms. Overall, these results may explain the diversity previously ascribed to the complex mechanisms of IL-10 anti-inflammatory activity.
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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/3' Untranslated Regions,
http://linkedlifedata.com/resource/pubmed/chemical/5' Untranslated Regions,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Immunosuppressive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Zymosan,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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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 |
15
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pubmed:volume |
168
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4837-45
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11994432-3' Untranslated Regions,
pubmed-meshheading:11994432-5' Untranslated Regions,
pubmed-meshheading:11994432-Adenoviridae,
pubmed-meshheading:11994432-Cells, Cultured,
pubmed-meshheading:11994432-Enzyme Activation,
pubmed-meshheading:11994432-Enzyme Inhibitors,
pubmed-meshheading:11994432-Gene Expression Regulation,
pubmed-meshheading:11994432-Genes, Reporter,
pubmed-meshheading:11994432-Humans,
pubmed-meshheading:11994432-Immunosuppressive Agents,
pubmed-meshheading:11994432-Interleukin-10,
pubmed-meshheading:11994432-Lipopolysaccharides,
pubmed-meshheading:11994432-Macrophages,
pubmed-meshheading:11994432-Mitogen-Activated Protein Kinases,
pubmed-meshheading:11994432-NF-kappa B,
pubmed-meshheading:11994432-Promoter Regions, Genetic,
pubmed-meshheading:11994432-RNA, Messenger,
pubmed-meshheading:11994432-RNA Stability,
pubmed-meshheading:11994432-Tumor Necrosis Factor-alpha,
pubmed-meshheading:11994432-Zymosan,
pubmed-meshheading:11994432-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2002
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pubmed:articleTitle |
Evidence for a dual mechanism for IL-10 suppression of TNF-alpha production that does not involve inhibition of p38 mitogen-activated protein kinase or NF-kappa B in primary human macrophages.
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pubmed:affiliation |
Kennedy Institute of Rheumatology Division, Imperial College Faculty of Medicine, Charing Cross Campus, 1 Aspenlea Road, London, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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