Effect of peroxisome proliferator-activated receptor γ on the cholesterol efflux of peritoneal macrophages in inflammation.
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 γ (PPARγ) 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 PPARγ antisense oligonucleotide group. The expression of PPARγ and nuclear factor of κ light polypeptide gene enhancer in B‑cells inhibitor α (IκBα) 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 PPARγ between the control group and ciglitazone group was observed. The expression levels of PPARγ in the PPARγ antisense oligonucleotide group were evidently lower than those in the control group. Subsequent to stimulation with LPS, the expression levels of PPARγ in the three groups were higher than those of each group prior to stimulation. The cholesterol efflux of the PPARγ antisense oligonucleotide group was clearly suppressed following stimulation with LPS in comparison with that of the other groups. PPARγ contributes to anti-inflammation by protecting IκBα from being phosphorylated and degraded and promoting cholesterol efflux from peritoneal macrophages in inflammation.
Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
Kun
K
He
Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
Yue
Y
Li
Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
Kang
K
Yang
Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
Jian-Ping
JP
Gong
Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
Pei-Zhi
PZ
Li
D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D020672:I-kappa B Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000072000:NF-KappaB Inhibitor alpha; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology
D007004:Hypoglycemic Agents; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; C000606205:Nfkbia protein, mouse; D016376:Oligonucleotides, Antisense; D047495:PPAR gamma; D045162:Thiazolidinediones; D000072000:NF-KappaB Inhibitor alpha; D002784:Cholesterol; C039671:ciglitazone