Linked Life Data

17158876

Source:http://linkedlifedata.com/resource/pubmed/id/17158876

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2007-2-12
pubmed:abstractText
The liver receptor homolog-1 (LRH-1) is an orphan nuclear receptor believed to play a key role in bile acid metabolism, cholesterol homeostasis, and intestinal cell crypt renewal. LRH-1 has recently been reported to negatively regulate the hepatic acute phase response by antagonizing, at least in part, the CCAAT/enhancer-binding protein signaling pathway. Here we have shown, using adenovirus-mediated LRH-1 overexpression and gene-silencing experiments, that the interleukin-1 receptor antagonist (IL-1RA) gene is a novel LRH-1 target gene in hepatic cells. Promoter mapping and chromatin immunoprecipitation experiments revealed that LRH-1 regulates IL-1RA gene expression under inflammatory conditions at the transcriptional level via the binding to an LRH-1 response element. Interestingly, IL-1RA induction by an intraperitoneal injection of lipopolysaccharide is significantly lower in LRH-1 heterozygous compared with wild-type mice, demonstrating the contribution of LRH-1 in IL-1RA gene regulation. Finally, RNA interference experiments indicate that LRH-1 blocks the hepatic acute phase response by, at least in part, inducing IL-1RA expression. Taken together, these results lead to the identification of IL-1RA as a novel LRH-1 target gene and demonstrate the existence of multiple mechanisms contributing to the overall anti-inflammatory properties of LRH-1 in hepatic cells.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4393-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17158876-Acute-Phase Reaction, pubmed-meshheading:17158876-Adenoviridae, pubmed-meshheading:17158876-Animals, pubmed-meshheading:17158876-CCAAT-Binding Factor, pubmed-meshheading:17158876-Cell Line, Tumor, pubmed-meshheading:17158876-DNA-Binding Proteins, pubmed-meshheading:17158876-Female, pubmed-meshheading:17158876-Gene Expression Regulation, pubmed-meshheading:17158876-Gene Silencing, pubmed-meshheading:17158876-Humans, pubmed-meshheading:17158876-Interleukin 1 Receptor Antagonist Protein, pubmed-meshheading:17158876-Lipopolysaccharides, pubmed-meshheading:17158876-Liver, pubmed-meshheading:17158876-Mice, pubmed-meshheading:17158876-Promoter Regions, Genetic, pubmed-meshheading:17158876-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:17158876-Signal Transduction, pubmed-meshheading:17158876-Transcription, Genetic, pubmed-meshheading:17158876-Transcription Factors
pubmed:year
2007
pubmed:articleTitle
Interleukin-1 receptor antagonist induction as an additional mechanism for liver receptor homolog-1 to negatively regulate the hepatic acute phase response.
pubmed:affiliation
Cardiovascular and Urogenital Center of Excellence for Drug Discovery, GlaxoSmithKline, 25 Avenue du Quebec, 91951 Les Ulis, France.
pubmed:publicationType
Journal Article, Comparative Study