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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
1999-6-7
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pubmed:abstractText |
In order to understand the molecular basis of the synergistic action of interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) on rat oligodendrocyte development, we studied some aspects of the signalling pathways involved in the regulation of the major histocompatibility complex (MHC) class I and the interferon regulatory factor 1 (IRF-1) gene expression. Two well-defined inducible enhancers of the MHC class I gene promoter, the MHC class I regulatory element (MHC-CRE) and the interferon consensus sequence (ICS), were analysed. Neither IFN-gamma nor TNF-alpha was capable of inducing MHC-CRE binding activity when administrated alone. Following the exposure of oligodendrocytes to IFN-gamma, TNF-R1 expression was transcriptionally induced by the binding of signal transducer and activator of transcription (STAT-1) homodimers to the IFN-gamma activated site (GAS) present in the gene promoter. The upregulation of TNF-R1 allowed TNF-alpha to induce the binding of nuclear factor-kappaB (NF-kappaB) to the MHC-CRE site. With respect to ICS element, IFN-gamma induced IRF-1 binding, that was further enhanced upon co-treatment with TNF-alpha. The existence of a synergism between IFN-gamma and TNF-alpha in stimulating IRF-1 expression at the transcriptional level was supported by IRF-1 promoter analysis: IFN-gamma directly induced the binding of STAT-1 homodimers to the GAS element, while NF-kappaB binding to the kappaB sequence was activated by TNF-alpha only after IFN-gamma treatment. This transcriptional regulation of IRF-1 gene by IFN-gamma and TNF-alpha was confirmed at the mRNA level. The synergism demonstrated in the present study highlights the importance of cytokine interactions in magnifying their biological effects during brain injury and inflammation.
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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/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Irf1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Stat1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0953-816X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2975-83
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:9758167-Animals,
pubmed-meshheading:9758167-Antigens, CD,
pubmed-meshheading:9758167-Base Sequence,
pubmed-meshheading:9758167-Cells, Cultured,
pubmed-meshheading:9758167-DNA-Binding Proteins,
pubmed-meshheading:9758167-Drug Synergism,
pubmed-meshheading:9758167-Gene Expression Regulation,
pubmed-meshheading:9758167-Genes, MHC Class I,
pubmed-meshheading:9758167-Interferon Regulatory Factor-1,
pubmed-meshheading:9758167-Interferon-gamma,
pubmed-meshheading:9758167-Molecular Sequence Data,
pubmed-meshheading:9758167-Oligodendroglia,
pubmed-meshheading:9758167-Phosphoproteins,
pubmed-meshheading:9758167-Rats,
pubmed-meshheading:9758167-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:9758167-Receptors, Tumor Necrosis Factor, Type I,
pubmed-meshheading:9758167-STAT1 Transcription Factor,
pubmed-meshheading:9758167-Signal Transduction,
pubmed-meshheading:9758167-Trans-Activators,
pubmed-meshheading:9758167-Transcription Factors,
pubmed-meshheading:9758167-Tumor Cells, Cultured,
pubmed-meshheading:9758167-Tumor Necrosis Factor-alpha
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pubmed:year |
1998
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pubmed:articleTitle |
Synergistic stimulation of MHC class I and IRF-1 gene expression by IFN-gamma and TNF-alpha in oligodendrocytes.
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pubmed:affiliation |
Laboratory of Organ and System Pathophysiology, Istituto Superiore di Sanità, Rome, Italy. neurobio@iss.it
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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