KMID : 0043320100330091443
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Archives of Pharmacal Research 2010 Volume.33 No. 9 p.1443 ~ p.1449
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Activation of LXR¥á induces lipogenesis in HaCaT cells
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Hong Il
Rho Ho-Sik Kim Duck-Hee Lee Mi-Ock
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Abstract
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The oxysterol nuclear receptors, LXR¥á (liver X receptor ¥á; NR1H3) and LXR¥â (NR1H2), coordinately regulate the expression of genes involved in lipid metabolism, anti-inflammation, and cholesterol transport. Previous studies have demonstrated that ligands of LXR¥á are important in the maintenance of the normal epidermal barrier function and keratinocyte differentiation. In this study, we examined whether LXR¥á and its ligands regulate lipid synthesis in HaCaT cells, a spontaneously transformed human keratinocyte cell line. When HaCaT cells were treated with the LXR¥á ligand TO901317, lipid droplets accumulated in the majority of cells, which were stained by Oil Red O. A luciferase reporter construct containing the LXR response element was activated about fourfold in HaCaT cells by TO901317 treatment, suggesting that LXR has a role in lipid synthesis in these cells. The expression of LXR¥á target genes, such as those encoding sterol regulatory binding protein and fatty acid synthase, were induced time dependently by TO901317, as measured by RT-PCR and western blotting. The expression of PPAR-¥á, -¥â, and -¥ã which regulate lipid metabolism, was also increased by TO901317 treatment. In contrast, TO901317 reduced the lipopolysaccharide-induced expression of cyclooxygenase 2 and inducible nitric oxide synthase in HaCaT cells. These results indicate that LXR¥á activation leads to lipogenesis in keratinocytes, which may enhance the epidermal barrier function of the skin.
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KEYWORD
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LXR, HaCaT, Lipid metabolism, Inflammation
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