title: Expression of liver X receptor alpha and lipid metabolism in granulocyte-macrophage colony-stimulating factor-induced human monocyte-derived macrophage.
abstract: 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 (Mvarphi) is considered a critical process in atherosclerotic lesions. The relationship, however, of the foam cell transformation of Mvarphi and LXR is not fully understood. The purpose of the present study was to examine the expression of LXRalpha, retinoid X receptor (RXR)alpha, ATP-binding cassette transporter (ABCA1), and macrophage scavenger receptor A (MSR-A), and lipid accumulation in human monocyte-derived Mvarphi. The expression of LXRalpha, ABCA1, MSR-A in 7 day cultured granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced Mvarphi (GM-Mvarphi) was significantly higher than that in 7 day cultured M-CSF-induced Mvarphi (M-Mvarphi). The expression levels of LXRalpha, ABCA1 and MSR-A protein decreased from 48 h to 5 days after the addition of lipopolysaccharide (LPS) in GM-Mvarphi, but only MSR-A protein decreased at 5 days after the addition of LPS in M-Mvarphi. Intracellular lipid accumulation was clearly observed when GM-Mvarphi 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 LXRalpha, ABCA1 and MSR-A by LPS may be related to the transformation of Mvarphis, especially GM-Mvarphi into foam cells.
authors.affiliation: Division of Cellular and Molecular Pathology, Department of Cellular Function, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kazawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawasaki
authors.forename: Azusa
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Masaru
authors.initials: M
authors.lastname: Imamura
authors.forename: Riuko
authors.initials: R
authors.lastname: Ohashi
authors.forename: Shuying
authors.initials: S
authors.lastname: Jiang
authors.forename: Toshiya
authors.initials: T
authors.lastname: Tanaka
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iwanari
authors.forename: Takao
authors.initials: T
authors.lastname: Hamakubo
authors.forename: Juro
authors.initials: J
authors.lastname: Sakai
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Makoto
authors.initials: M
authors.lastname: Naito
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005487:Foam Cells / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D050356:Lipid Metabolism / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics; D047488:Retinoid X Receptors / Q000096:biosynthesis / Q000235:genetics; D051117:Scavenger Receptors, Class A / Q000096:biosynthesis / Q000235:genetics
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D000071518:Liver X Receptors; C495139:MSR1 protein, human; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D047488:Retinoid X Receptors; D051117:Scavenger Receptors, Class A; D016178:Granulocyte-Macrophage Colony-Stimulating Factor