Liver X Receptor (LXR) Regulation of the LXRα Gene in Human Macrophages
| Autor: | Steven A. Kliewer, Timothy M. Willson, Cristin M. Galardi, Jodi M. Maglich, Bryan Goodwin, Karl Whitney, Michael A. Watson, Joan G. Wilson, Jon L. Collins |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Receptors Retinoic Acid Receptors Cytoplasmic and Nuclear Biology Biochemistry Cell Line Mice chemistry.chemical_compound Transcription (biology) polycyclic compounds Animals Humans Liver X receptor Molecular Biology Gene Liver X Receptors Receptors Thyroid Hormone Base Sequence Sequence Homology Amino Acid Catabolism Cholesterol Macrophages Reverse cholesterol transport Transporter DNA Cell Biology Orphan Nuclear Receptors Cell biology DNA-Binding Proteins Mice Inbred C57BL Gene Expression Regulation chemistry Cell culture Mutagenesis Site-Directed lipids (amino acids peptides and proteins) |
| Zdroj: | Journal of Biological Chemistry. 276:43509-43515 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m106155200 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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