Linked Life Data

11679413

Source:http://linkedlifedata.com/resource/pubmed/id/11679413

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2001-10-26
pubmed:abstractText
The functional interaction, or "cross-talk," between estrogen receptor (ER) and the proinflammatory transcription factor nuclear factor (NF)-kappaB demonstrated in vitro has been suggested to play a role in estrogen prevention of cardiovascular disease. Here, we demonstrate that this reciprocal cross-talk occurs in vivo. Ovariectomized C57BL/6 mice fed an atherogenic diet had increased hepatic levels of active NF-kappaB and numerous inflammatory genes, including MHC invariant chain (Ii), vascular cell adhesion molecule-1, tumor necrosis factor-alpha, and RANTES. Treatment with 17alpha-ethinylestradiol (EE) strongly blocked induction of these genes but had no effect on their basal expression levels. ER was required for this activity, because the antagonist ICI 182,780 completely blocked the inhibitory activity of EE. Gene activation by EE was not required for inhibition of inflammatory gene expression, because both the phytoestrogen genistein and low doses of EE were effective in blocking inflammatory gene induction without inducing marker genes such as intestinal trefoil factor (ITF) or myo-inositol-1-phosphate synthase (IPS). The in vivo transcriptional interference was reciprocal, with EE induction of ITF and IPS greatly reduced in animals fed the atherogenic diet versus chow-fed controls. This interference was specific to the liver, because diet had no effect on uterine weight increases produced by EE. Transfection experiments confirmed that the extent of inhibition of ER-mediated transcription by inflammatory stimuli correlated with the extent of NF-kappaB activation. These results suggest that the cross-talk between ER and NF-kappaB does occur in vivo and may indeed contribute significantly to the cardioprotective effects of estrogen.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
26
pubmed:volume
89
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
823-30
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11679413-Animals, pubmed-meshheading:11679413-Cell Line, pubmed-meshheading:11679413-Coronary Artery Disease, pubmed-meshheading:11679413-Diet, Atherogenic, pubmed-meshheading:11679413-Disease Models, Animal, pubmed-meshheading:11679413-Dose-Response Relationship, Drug, pubmed-meshheading:11679413-Enzyme Inhibitors, pubmed-meshheading:11679413-Estradiol Congeners, pubmed-meshheading:11679413-Estrogen Replacement Therapy, pubmed-meshheading:11679413-Ethinyl Estradiol, pubmed-meshheading:11679413-Female, pubmed-meshheading:11679413-Gene Expression Regulation, pubmed-meshheading:11679413-Genes, Reporter, pubmed-meshheading:11679413-Genistein, pubmed-meshheading:11679413-Inflammation, pubmed-meshheading:11679413-Liver, pubmed-meshheading:11679413-Mice, pubmed-meshheading:11679413-Mice, Inbred C57BL, pubmed-meshheading:11679413-NF-kappa B, pubmed-meshheading:11679413-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:11679413-Ovariectomy, pubmed-meshheading:11679413-RNA, Messenger, pubmed-meshheading:11679413-Receptors, Estrogen, pubmed-meshheading:11679413-Recombinant Fusion Proteins, pubmed-meshheading:11679413-Transcriptional Activation, pubmed-meshheading:11679413-Transfection
pubmed:year
2001
pubmed:articleTitle
Reciprocal antagonism between estrogen receptor and NF-kappaB activity in vivo.
pubmed:affiliation
Women's Health Research/Cardiovascular, Wyeth-Ayerst Research, Radnor, PA 19087, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't