Resveratrol regulates the expression of LXR-alpha in human macrophages.
The naturally occurring polyphenol resveratrol has been associated with the beneficial effects of red wine consumption on cardiovascular disease and shown to inhibit atherosclerosis in animal models. To determine if resveratrol affects the expression of genes that control lipid homeostasis in human macrophages, we measured expression changes in the LXR-alpha pathway, crucial to cholesterol efflux, and in genes that mediate lipoprotein uptake. Resveratrol treatment of THP-1 macrophages induced LXR-alpha at mRNA and protein levels. Increased recruitment of RNA polymerase II to the LXR-alpha promoter suggested that up-regulation was at least partly mediated by transcriptional mechanisms. Resveratrol also induced LXR-alpha in human monocyte-derived macrophages together with elevated ABCA1 and ABCG1 mRNA levels. Moreover, resveratrol repressed the expression of the lipid uptake genes LPL and SR-AII. The ability of resveratrol to modulate expression of the genes involved in lipid uptake and efflux suggests that polyphenols can potentially limit cholesterol accumulation in human macrophages.
Sevov
Marie
M
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Sweden.
Elfineh
Lioudmila
L
Cavelier
Lucia B
LB
D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics*; D000071518:Liver X Receptors; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013267:Stilbenes; D000077185:Resveratrol