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

First Author  Whitney KD Year  2001
Journal  J Biol Chem Volume  276
Issue  47 Pages  43509-15
PubMed ID  11546778 Mgi Jnum  J:72768
Mgi Id  MGI:2153575 Doi  10.1074/jbc.M106155200
Citation  Whitney KD, et al. (2001) Liver X Receptor (LXR) Regulation of the LXRalpha Gene in Human Macrophages. J Biol Chem 276(47):43509-15
abstractText  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.
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