Abstract
Liver X receptors alpha (LXRα) and beta (LXRβfunction as physiological sensors of cholesterol metabolites (oxysterols), regulating key genes involved in cholesterol and lipid metabolism. LXRs have been extensively studied in both human and rodent cell systems, revealing their potential therapeutic value in the contexts of atherosclerosis and inflammatory diseases. The LXR genome landscape has been investigated in murine macrophages but not in human THP-1 cells, which represent one of the frequently employed monocyte/macrophage cell systems to study immune responses. We used a whole genome screen to detect direct LXR target genes in THP-1 cells treated with two widely used LXR ligands (T0901317 and GW3965). This screen identified the sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) gene as a novel LXR regulated gene, with an LXR response element (LXRE) within its promoter. We investigated the regulation of SMPDL3A gene expression by LXRs across several human and mouse cell types. These studies indicate that the induction of SMDPL3A is LXR-dependent and is restricted to human blood cells with no induction observed in mouse cellular systems.
- Regulation of gene expression
- Regulation - transcriptional
- Leukocytes/Mast cells
- Cholesterol metabolism/lipoproteins
- Received March 22, 2012.
- Revision received July 11, 2012.
- Accepted July 11, 2012.
- The American Society for Pharmacology and Experimental Therapeutics