Effect of Peroxisome Proliferator-Activated Receptor Γ on the Cholesterol Efflux of Peritoneal Macrophages in Inflammation
Molecular Medicine Reports(2014)
摘要
Atherosclerosis, a chronic inflammatory disorder characterized by lipid and cholesterol accumulation, is the principal contributing factor to the pathology of cardiovascular disease. Macrophages contribute to plaque development by internalizing native and modified lipoproteins that convert them into cholesterol-rich foam cells. With multiple factors, including hypercholesterolemia and inflammation, promoting atherosclerosis, it is of great significance to elucidate how the mechanism of cholesterol efflux from the macrophages changes and the role of peroxisome proliferator-activated receptor gamma (PPAR gamma) in these situations. Following isolation and culture of peritoneal macrophages from C57BL/6 mice in the present study, the cells were divided into three groups: The control group, the ciglitazone group and the PPAR gamma antisense oligonucleotide group. The expression of PPAR gamma and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (I kappa B alpha) in each group was observed through the levels of protein and mRNA, and then the cholesterol efflux of each group was investigated. In addition, the same experiments were repeated following stimulation of each group with lipopolysaccharide (LPS). No significant difference in the expression levels of PPAR gamma between the control group and ciglitazone group was observed. The expression levels of PPAR gamma in the PPAR gamma antisense oligonucleotide group were evidently lower than those in the control group. Subsequent to stimulation with LPS, the expression levels of PPAR gamma in the three groups were higher than those of each group prior to stimulation. The cholesterol efflux of the PPAR gamma antisense oligonucleotide group was clearly suppressed following stimulation with LPS in comparison with that of the other groups. PPAR gamma contributes to anti-inflammation by protecting I kappa B alpha from being phosphorylated and degraded and promoting cholesterol efflux from peritoneal macrophages in inflammation.
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关键词
peroxisome proliferator-activated receptor gamma,cholesterol efflux,peritoneal macrophage
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