Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-4-16
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0014-4827
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
239
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
423-9
pubmed:dateRevised
2008-11-21
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
pubmed:year
1998
pubmed:articleTitle
TNF-alpha and 9-cis-retinoic acid synergistically induce ICAM-1 expression: evidence for interaction of retinoid receptors with NF-kappa B.
pubmed:affiliation
Department of Reproductive Endocrinology, Women's Health Research Institute, Wyeth-Ayerst Research, Radnor, Pennsylvania 19087, USA.
pubmed:publicationType
Journal Article