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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
1998-10-22
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pubmed:abstractText |
Monocyte chemoattractant protein-1 (MCP-1) is induced in chronic osseous inflammation, and is temporally and spatially correlated with monocyte recruitment. We investigated the mechanism of MCP-1 regulation in a human osteoblastic cell line in response to IFN-gamma, a potent mediator of the immune inflammatory response. Nuclear run-on and stability studies demonstrated that IFN-gamma stimulated MCP-1 transcription and did not enhance mRNA stabilization. Using MCP-1 promoter/reporter gene constructs, we determined that IFN-gamma-enhanced MCP-1 transcription is regulated by a 29-bp element located at -227 relative to the ATG start codon. This element contains a 13-bp CT-rich sequence (GCTTCCCTTTCCT) adjacent to a IFN-gamma activation site (GAS). Since deletion of the CT sequence enhanced both the magnitude and duration of IFN-gamma-stimulated, GAS-mediated transcription, we have termed it the IFN response-inhibitory sequence (IRIS). The combined IRIS/GAS sequence is highly conserved in mouse, rat, and bovine MCP-1 genes. In gel-shift assays, nuclear extracts from IFN-gamma-stimulated osteoblastic cells formed two specific inducible bands with labeled IRIS/GAS DNA. Both bands were supershifted by anti-STAT1 Abs, but not by Abs to STAT2, p48(ISGF-3y), IFN-regulatory factor-1, or IFN-regulatory factor-2. Formation of one of the bands required the presence of the IRIS moiety. IRIS/GAS DNA also formed a number of specific complexes with constitutively expressed factors, none of which were affected by the above Abs. These studies establish a mechanism for IFN-gamma-stimulated MCP-1 expression and identify a complex element that regulates MCP-1 gene transcription.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL2,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
161
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3719-28
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:9759897-Base Sequence,
pubmed-meshheading:9759897-Chemokine CCL2,
pubmed-meshheading:9759897-Conserved Sequence,
pubmed-meshheading:9759897-DNA-Binding Proteins,
pubmed-meshheading:9759897-Evolution, Molecular,
pubmed-meshheading:9759897-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:9759897-Humans,
pubmed-meshheading:9759897-Interferon-gamma,
pubmed-meshheading:9759897-Molecular Sequence Data,
pubmed-meshheading:9759897-Nuclear Proteins,
pubmed-meshheading:9759897-Osteoblasts,
pubmed-meshheading:9759897-Promoter Regions, Genetic,
pubmed-meshheading:9759897-Transcription, Genetic,
pubmed-meshheading:9759897-Transcription Factors,
pubmed-meshheading:9759897-Tumor Cells, Cultured
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pubmed:year |
1998
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pubmed:articleTitle |
A complex element regulates IFN-gamma-stimulated monocyte chemoattractant protein-1 gene transcription.
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pubmed:affiliation |
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7870, USA. valente@uthscsa.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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