title: Synergistic effect of scavenger receptor A and low-density lipoprotein receptor on macrophage foam cell formation under inflammatory stress.
abstract: To provide experimental evidence for the effect of inflammation on cholesterol accumulation in macrophages, we investigated the expression of low-density lipoprotein receptor (LDL-R) and scavenger receptor A (SR-A) genes and proteins in the lipopolysaccharide (LPS)-stimulated macrophage-like RAW264.7 cell line. RAW264.7 cells were incubated in serum-free medium in the absence or presence of LDL alone, LDL+LPS and LPS alone. Intracellular cholesterol content, tumor necrosis factor α levels in the supernatants, mRNA and protein expression of LDL-R and SR-A in the treated cells were assessed by Oil Red O staining cholesterol enzymatic assay, enzyme-linked immunosorbent assay, semi-quantitative polymerase chain reaction and western blot analysis, respectively. Our results demonstrated that LPS was able to upregulate SR-A mRNA and protein expression, override LDL-R suppression induced by a high dose of LDL and increase LDL uptake by enhancing receptor expression, leading to foam cell formation in RAW264.7 cells. These findings suggest that the synergy of the upregulation of SR-A and dysregulation of LDL-R under inflammatory stress may contribute to macrophage-derived foam cell formation.
authors.affiliation: Chongqing Key Laboratory of Hepatobiliary Surgery and Department of Hepatobiliary Surgery, Second Affiliated Hospital to Chongqing Medical University, Chongqing, PR China.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Su
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Xiongzhong
authors.initials: X
authors.lastname: Ruan
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zuo
authors.forename: Jianping
authors.initials: J
authors.lastname: Gong
mesh_terms: D000818:Animals; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D005487:Foam Cells / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D011973:Receptors, LDL; D051117:Scavenger Receptors, Class A; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol