Liver X Receptor (LXR) Regulation of the LXRα Gene in Human Macrophages

Karl D. Whitney, Michael A. Watson, Bryan Goodwin, Cristin M. Galardi, Jodi M. Maglich, Joan G. Wilson, Timothy M. Willson, Jon L. Collins, Steven A. Kliewer

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

The nuclear oxysterol receptors LXRα (NR1H3) and LXRβ (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 LXRα 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 LXRα gene was isolated, and the transcription initiation site delineated. Analysis of the LXRα promoter revealed a functional LXR/RXR binding site ∼2.9 kb upstream of the transcription initiation site. We conclude that LXRα 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.

Original languageEnglish (US)
Pages (from-to)43509-43515
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number47
DOIs
StatePublished - Nov 23 2001

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Macrophages
Liver
Genes
Transcription Initiation Site
Cholesterol
Cells
Liver X Receptors
Gene encoding
Cell Line
Foam Cells
Transcription
Adipocytes
Foams
Hepatocytes
Atherosclerosis
Binding Sites
Tissue
Ligands
Lipids
Gene Expression

ASJC Scopus subject areas

  • Biochemistry

Cite this

Whitney, K. D., Watson, M. A., Goodwin, B., Galardi, C. M., Maglich, J. M., Wilson, J. G., ... Kliewer, S. A. (2001). Liver X Receptor (LXR) Regulation of the LXRα Gene in Human Macrophages. Journal of Biological Chemistry, 276(47), 43509-43515. https://doi.org/10.1074/jbc.M106155200

Liver X Receptor (LXR) Regulation of the LXRα Gene in Human Macrophages. / Whitney, Karl D.; Watson, Michael A.; Goodwin, Bryan; Galardi, Cristin M.; Maglich, Jodi M.; Wilson, Joan G.; Willson, Timothy M.; Collins, Jon L.; Kliewer, Steven A.

In: Journal of Biological Chemistry, Vol. 276, No. 47, 23.11.2001, p. 43509-43515.

Research output: Contribution to journalArticle

Whitney, KD, Watson, MA, Goodwin, B, Galardi, CM, Maglich, JM, Wilson, JG, Willson, TM, Collins, JL & Kliewer, SA 2001, 'Liver X Receptor (LXR) Regulation of the LXRα Gene in Human Macrophages', Journal of Biological Chemistry, vol. 276, no. 47, pp. 43509-43515. https://doi.org/10.1074/jbc.M106155200
Whitney KD, Watson MA, Goodwin B, Galardi CM, Maglich JM, Wilson JG et al. Liver X Receptor (LXR) Regulation of the LXRα Gene in Human Macrophages. Journal of Biological Chemistry. 2001 Nov 23;276(47):43509-43515. https://doi.org/10.1074/jbc.M106155200
Whitney, Karl D. ; Watson, Michael A. ; Goodwin, Bryan ; Galardi, Cristin M. ; Maglich, Jodi M. ; Wilson, Joan G. ; Willson, Timothy M. ; Collins, Jon L. ; Kliewer, Steven A. / Liver X Receptor (LXR) Regulation of the LXRα Gene in Human Macrophages. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 47. pp. 43509-43515.
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