RGD Reference Report - Liver X receptor (LXR) regulation of the LXRalpha gene in human macrophages. - Rat Genome Database

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Liver X receptor (LXR) regulation of the LXRalpha gene in human macrophages.

Authors: Whitney, K D  Watson, M A  Goodwin, B  Galardi, C M  Maglich, J M  Wilson, J G  Willson, T M  Collins, J L  Kliewer, S A 
Citation: Whitney KD, etal., J Biol Chem. 2001 Nov 23;276(47):43509-15. doi: 10.1074/jbc.M106155200. Epub 2001 Aug 23.
RGD ID: 401842375
Pubmed: PMID:11546778   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M106155200   (Journal Full-text)

The nuclear oxysterol receptors LXRalpha (NR1H3) and LXRbeta (NR1H2) coordinately regulate the expression of genes involved in the transport and catabolism of cholesterol. In macrophages, LXR stimulates the transcription of genes encoding transporters involved in cholesterol efflux, which may limit the transformation of these cells into foam cells in response to lipid loading. Here, we report that natural and synthetic LXR ligands induce the expression of the LXRalpha gene in primary human macrophages and differentiated THP-1 macrophages. This regulation was not observed in primary human adipocytes or hepatocytes, a human intestinal cell line, or in any mouse tissue or cell line examined. The human LXRalpha gene was isolated, and the transcription initiation site delineated. Analysis of the LXRalpha promoter revealed a functional LXR/RXR binding site approximately 2.9 kb upstream of the transcription initiation site. We conclude that LXRalpha regulates its own expression in human macrophages and that this response is likely to amplify the effects of oxysterols on reverse cholesterol transport. These findings underscore the importance of LXR as a potential therapeutic target for the treatment of atherosclerosis.



Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NR1H3Human(22R)-22-hydroxycholesterol increases expression EXP 22(R)-hydroxycholesterol increases expression of NR1H3 mRNA in macrophagesRGD 
Nr1h3Rat(22R)-22-hydroxycholesterol increases expression ISONR1H3 (Homo sapiens)22(R)-hydroxycholesterol increases expression of NR1H3 mRNA in macrophagesRGD 
Nr1h3Mouse(22R)-22-hydroxycholesterol increases expression ISONR1H3 (Homo sapiens)22(R)-hydroxycholesterol increases expression of NR1H3 mRNA in macrophagesRGD 
NR1H3Human24(S),25-epoxycholesterol increases expression EXP 24(S) and 25-epoxycholesterol increases expression of NR1H3 mRNA in macrophagesRGD 
Nr1h3Rat24(S),25-epoxycholesterol increases expression ISONR1H3 (Homo sapiens)24(S) and 25-epoxycholesterol increases expression of NR1H3 mRNA in macrophagesRGD 
Nr1h3Mouse24(S),25-epoxycholesterol increases expression ISONR1H3 (Homo sapiens)24(S) and 25-epoxycholesterol increases expression of NR1H3 mRNA in macrophagesRGD 

Objects Annotated

Genes (Rattus norvegicus)
Nr1h3  (nuclear receptor subfamily 1, group H, member 3)

Genes (Mus musculus)
Nr1h3  (nuclear receptor subfamily 1, group H, member 3)

Genes (Homo sapiens)
NR1H3  (nuclear receptor subfamily 1 group H member 3)


Additional Information