Expression of liver X receptor α and lipid metabolism in granulocyte-macrophage colony-stimulating factor-induced human monocyte-derived macrophage

Liver X receptor (LXR) is a nuclear receptor that acts as a sterol sensor and metabolic regulator of cholesterol and lipid homeostasis. The foam cell transformation of macrophages (Mφ) is considered a critical process in atherosclerotic lesions. The relationship, however, of the foam cell transformation of Mφ and LXR is not fully understood. The purpose of the present study was to examine the expression of LXRα, retinoid X receptor (RXR)α, ATP-binding cassette transporter (ABCA1), and macrophage scavenger receptor A (MSR-A), and lipid accumulation in human monocyte-derived Mφ. The expression of LXRα, ABCA1, MSR-A in 7 day cultured granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced Mφ (GM-Mφ) was significantly higher than that in 7 day cultured M-CSF-induced Mφ (M-Mφ). The expression levels of LXRα, ABCA1 and MSR-A protein decreased from 48 h to 5 days after the addition of lipopolysaccharide (LPS) in GM-Mφ, but only MSR-A protein decreased at 5 days after the addition of LPS in M-Mφ. Intracellular lipid accumulation was clearly observed when GM-Mφ was pre-stimulated with LPS for 48 h and incubated with oxidized LDL for an additional 5 days. These findings suggest that the inhibitory activity of LXRα, ABCA1 and MSR-A by LPS may be related to the transformation of Mφs, especially GM-Mφ into foam cells.