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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
1998-5-4
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pubmed:abstractText |
We analyzed the molecular mechanisms by which IL-12 and IL-18 induce transcriptional activity of the IFN-gamma promoter in primary human CD4+ T cells. In transfection experiments, we found that IL-18 directly induces IFN-gamma promoter activity, whereas significant activation with IL-12 required costimulation with alphaCD3/CD28. Furthermore, IL-12 caused in vivo protection of a STAT4 (-236) binding site, whereas stimulation with IL-18 or IL-12 plus alphaCD3/CD28 induced occupancy of a downstream AP-1 site. Mutation of this AP-1 site abrogated both IL-12- and IL-18-mediated promoter activation, whereas mutation of the STAT site inhibited IL-12-dependent activation. These data suggest that both AP-1 and STAT4 are required for IL-12-dependent IFN-gamma promoter activity, whereas IL-18 causes direct activation via AP-1. This differential activation of the IFN-gamma promoter gives further insights into molecular pathways governing Th1 T cell development and differentiation.
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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/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-18,
http://linkedlifedata.com/resource/pubmed/chemical/STAT4 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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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 |
160
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3642-7
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:9558063-Base Sequence,
pubmed-meshheading:9558063-Binding Sites,
pubmed-meshheading:9558063-CD4-Positive T-Lymphocytes,
pubmed-meshheading:9558063-Cells, Cultured,
pubmed-meshheading:9558063-Cytokines,
pubmed-meshheading:9558063-DNA Footprinting,
pubmed-meshheading:9558063-DNA Primers,
pubmed-meshheading:9558063-DNA-Binding Proteins,
pubmed-meshheading:9558063-Humans,
pubmed-meshheading:9558063-Interferon-gamma,
pubmed-meshheading:9558063-Interleukin-12,
pubmed-meshheading:9558063-Interleukin-18,
pubmed-meshheading:9558063-Models, Biological,
pubmed-meshheading:9558063-Mutagenesis, Site-Directed,
pubmed-meshheading:9558063-Polymerase Chain Reaction,
pubmed-meshheading:9558063-Promoter Regions, Genetic,
pubmed-meshheading:9558063-STAT4 Transcription Factor,
pubmed-meshheading:9558063-Trans-Activators,
pubmed-meshheading:9558063-Transcription Factor AP-1,
pubmed-meshheading:9558063-Transcriptional Activation,
pubmed-meshheading:9558063-Transfection
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pubmed:year |
1998
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pubmed:articleTitle |
IL-12 and IL-18 differentially regulate the transcriptional activity of the human IFN-gamma promoter in primary CD4+ T lymphocytes.
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pubmed:affiliation |
Laboratory of Immunology, I. Medical Clinic, University of Mainz, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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