Source:http://linkedlifedata.com/resource/pubmed/id/10358173
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
1999-6-30
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| pubmed:abstractText |
IL-12 is a critical immunoregulatory cytokine that promotes cell-mediated immune responses and the differentiation of naive CD4+ cells to Th1 cells; however, relatively few IL-12 target genes have been identified. To better clarify the molecular basis of IL-12 action, we set out to characterize genes up-regulated by IL-12, first by contrasting IL-12- and IFN-alpha-inducible genes. We identified several genes up-regulated by IL-12, namely, MIP-1alpha, MIP-1beta, IL-1RA, and IFN regulatory factor-1 (IRF-1). IRF-1 is a transcription factor regulated by IFNs that is also essential for Th1 responses. We demonstrated that IL-12 directly up-regulates IRF-1 to the same extent as IFN-alpha in normal human T cells and in NK cells. We showed that IL-12 had a direct effect on IRF-1, an effect not mediated indirectly by the induction of IFN-gamma production. Furthermore, IL-2 and IL-12 synergistically induced IRF-1, whereas IFN-alpha and IL-12 did not. The participation of STAT4 in the regulation of IRF-1 was demonstrated in two ways. First, STAT4 was required for the IL-12-dependent transactivation of an IRF-1 reporter construct, and second, STAT4 binding to the IRF-1 promoter was shown using EMSA. In contrast to IL-12, no up-regulation of IRF-1 was found in IL-4-stimulated cells, and IL-4 did not block IL-12-dependent up-regulation of IRF-1. Therefore, IRF-1 may be an important contributor to IL-12 signaling, and we speculate that the defective IL-12 responses seen in IRF-1-/- mice might be attributable, in part, to the absence of this transcription factor.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/IRF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Interferons,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12,
http://linkedlifedata.com/resource/pubmed/chemical/Irf1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/STAT4 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Stat4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
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| pubmed:issn |
0022-1767
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
162
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
7256-62
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| pubmed:dateRevised |
2005-11-17
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| pubmed:meshHeading |
pubmed-meshheading:10358173-3T3 Cells,
pubmed-meshheading:10358173-Animals,
pubmed-meshheading:10358173-Cell Line,
pubmed-meshheading:10358173-Cells, Cultured,
pubmed-meshheading:10358173-DNA-Binding Proteins,
pubmed-meshheading:10358173-Gene Expression Regulation,
pubmed-meshheading:10358173-Humans,
pubmed-meshheading:10358173-Interferon Regulatory Factor-1,
pubmed-meshheading:10358173-Interferon-alpha,
pubmed-meshheading:10358173-Interferons,
pubmed-meshheading:10358173-Interleukin-12,
pubmed-meshheading:10358173-Killer Cells, Natural,
pubmed-meshheading:10358173-Mice,
pubmed-meshheading:10358173-Phosphoproteins,
pubmed-meshheading:10358173-STAT4 Transcription Factor,
pubmed-meshheading:10358173-Signal Transduction,
pubmed-meshheading:10358173-T-Lymphocytes,
pubmed-meshheading:10358173-Trans-Activators,
pubmed-meshheading:10358173-Up-Regulation
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| pubmed:year |
1999
|
| pubmed:articleTitle |
IL-12 induces IFN regulating factor-1 (IRF-1) gene expression in human NK and T cells.
|
| pubmed:affiliation |
Lymphocyte Cell Biology Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal Diseases, Bethesda, MD 20892, USA.
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| pubmed:publicationType |
Journal Article
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