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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1998-4-16
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pubmed:abstractText |
TNF-alpha and 9-cis-retinoic acid (9-cis-R) synergistically enhance ICAM-1 protein expression in immortalized human aortic endothelial cells (HAECTs). At a TNF-alpha concentration of 0.1 ng/ml, 1 microM 9-cis-R enhanced ICAM-1 protein expression 4-fold. Treatment with 1 microM 9-cis-R alone caused no induction of ICAM-1 expression. Functional analysis of human ICAM-1 promoter-luciferase constructs revealed that the synergism was attributable to transcriptional regulation. Expression of a luciferase reporter vector containing a 311-bp fragment of the ICAM-1 promoter (-252 to + 59 bp relative to the transcriptional start site) was increased 2.9- and 4.9-fold by treatment with 9-cis-R and TNF-alpha, respectively, while cotreatment with 9-cis-R and TNF-alpha induced expression to 19.9-fold. Mutation studies revealed that RARE and NF-kappa B sites located respectively at -226 and -188 bp relative to the transcription start site are essential for the synergistic control of promoter activity. Mutation of either the RARE or the NF-kappa B site eliminated the synergistic enhancement of promoter activity. Moreover, mutation of the RARE abrogated promoter activity induced by treatment with TNF-alpha alone and mutation of the NF-kappa B site eliminated promoter activity induced by treatment with 9-cis-R alone. We conclude that retinoid receptors and NF-kappa B act in concert at the promoter level to facilitate ICAM-1 expression in endothelial cells.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Retinoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tretinoin,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Cell Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/alitretinoin
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0014-4827
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
239
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
423-9
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:9521860-Aorta,
pubmed-meshheading:9521860-Cell Adhesion,
pubmed-meshheading:9521860-Cell Line, Transformed,
pubmed-meshheading:9521860-Drug Synergism,
pubmed-meshheading:9521860-Endothelium, Vascular,
pubmed-meshheading:9521860-Female,
pubmed-meshheading:9521860-Genes, Reporter,
pubmed-meshheading:9521860-Humans,
pubmed-meshheading:9521860-Intercellular Adhesion Molecule-1,
pubmed-meshheading:9521860-Luciferases,
pubmed-meshheading:9521860-Middle Aged,
pubmed-meshheading:9521860-NF-kappa B,
pubmed-meshheading:9521860-Promoter Regions, Genetic,
pubmed-meshheading:9521860-Receptors, Retinoic Acid,
pubmed-meshheading:9521860-Recombinant Fusion Proteins,
pubmed-meshheading:9521860-Regulatory Sequences, Nucleic Acid,
pubmed-meshheading:9521860-Stimulation, Chemical,
pubmed-meshheading:9521860-Tretinoin,
pubmed-meshheading:9521860-Tumor Necrosis Factor-alpha,
pubmed-meshheading:9521860-Vascular Cell Adhesion Molecule-1
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pubmed:year |
1998
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pubmed:articleTitle |
TNF-alpha and 9-cis-retinoic acid synergistically induce ICAM-1 expression: evidence for interaction of retinoid receptors with NF-kappa B.
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pubmed:affiliation |
Department of Reproductive Endocrinology, Women's Health Research Institute, Wyeth-Ayerst Research, Radnor, Pennsylvania 19087, USA.
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pubmed:publicationType |
Journal Article
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