Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
1997-7-10
pubmed:abstractText
Estrogens are the most effective agents available for preventing osteoporosis, and their principal role in bone metabolism is the inhibition of interleukin-6 (IL-6) production in osteoblasts and bone marrow stromal cells. We examined the mechanism of inhibitory effect of estrogens on the 190 bp proximal promoter of the IL-6 gene. Promoter activity induced by transfection of both NF-kappaB p65 subunit and NF-IL6 was decreased by 45% by estradiol (E2)-estrogen receptor (ER) complexes. The inhibitory effect of E2 was also observed on a mutant IL-6 promoter in which the NF-IL6 binding site was disrupted. E2 repressed the wild-type promoter activity induced by NF-kappaB p65 subunit alone, but had no effect on that induced by NF-IL6 alone. These findings suggested that estrogens inhibit IL-6 production by interfering with the function of NF-kappaB rather than that of NF-IL6. The ER mutant, HE19, which does not contain the A/B domain, repressed the induction by NF-kappaB to the same extent as wild-type ER HE0, whereas the effect of C-terminal deletion mutant, HE21, was only marginal. The antiestrogen, 4-hydroxytamoxifen (OHT), had no effect on IL-6 promoter activity, suggesting that E2-induced conformational change of the hormone binding domain plays an important role in protein-protein interaction between ER and NF-kappaB. E2 had no effect on the nuclear translocation of NF-kappaB, and electrophoretic mobility shift assay showed that the presence of E2-ER complexes did not affect the ability of NF-kappaB to bind to specific DNA sequences.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/4-hydroxytamoxifen, http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Estradiol, http://linkedlifedata.com/resource/pubmed/chemical/Estrogen Antagonists, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6, http://linkedlifedata.com/resource/pubmed/chemical/Luciferases, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Tamoxifen
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0960-0760
pubmed:author
pubmed:issnType
Print
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9182853-Animals, pubmed-meshheading:9182853-Binding Sites, pubmed-meshheading:9182853-CCAAT-Enhancer-Binding Proteins, pubmed-meshheading:9182853-COS Cells, pubmed-meshheading:9182853-DNA-Binding Proteins, pubmed-meshheading:9182853-Estradiol, pubmed-meshheading:9182853-Estrogen Antagonists, pubmed-meshheading:9182853-Gene Expression Regulation, pubmed-meshheading:9182853-Genes, Reporter, pubmed-meshheading:9182853-Interleukin-6, pubmed-meshheading:9182853-Luciferases, pubmed-meshheading:9182853-Mutation, pubmed-meshheading:9182853-NF-kappa B, pubmed-meshheading:9182853-Nuclear Proteins, pubmed-meshheading:9182853-Plasmids, pubmed-meshheading:9182853-Promoter Regions, Genetic, pubmed-meshheading:9182853-Receptors, Estrogen, pubmed-meshheading:9182853-Recombinant Proteins, pubmed-meshheading:9182853-Tamoxifen, pubmed-meshheading:9182853-Transfection
pubmed:year
1997
pubmed:articleTitle
Characterization of mechanisms of interleukin-6 gene repression by estrogen receptor.
pubmed:affiliation
Department of Medicine III, Osaka University Medical School, Suita, Japan.
pubmed:publicationType
Journal Article