title: Involvement of peroxisome proliferator activated receptor-γ in the anti-inflammatory effects of atorvastatin in oxygen-glucose deprivation/reperfusion-stimulated RAW264.7 murine macrophages.
abstract: Ischemia‑reperfusion (I/R) injury is important in the pathogenesis and/or progression of various diseases, including stroke, cardiovascular disease and acute renal injury. Increasing evidence indicates that atorvastatin exerts protective effects in I/R injury‑associated diseases; however, the underlying mechanisms remain to be fully elucidated. In the present study, oxygen‑glucose deprivation (OGD)/reperfusion‑stimulated. RAW264.7 murine macrophages served as a model of I/R injury. The knockdown of peroxisome proliferator activated receptor‑γ (PPARγ) expression in these cells increased OGD/reperfusion‑induced expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor‑α (TNF‑α) and interferon‑γ (IFN‑γ), and enhanced OGD/reperfusion‑induced downregulation of the expression of cluster of differentiation (CD) 206, at the mRNA and protein levels. Conversely, overexpression of PPARγ significantly attenuated OGD/reperfusion‑induced alterations in the expression of iNOS, TNF‑α, IFN‑γ and CD206 at the mRNA and protein levels. Notably, atorvastatin inhibited OGD/reperfusion‑induced iNOS expression and reversed OGD/reperfusion‑induced downregulation of the expression of CD206 and PPARγ at the mRNA and protein levels. The results of the present study indicate that atorvastatin exhibits significant anti‑inflammatory effects in OGD/reperfusion‑stimulated RAW264.7 cells, possibly via PPARγ regulation. The findings of the present study may reveal a novel mechanism underlying the protective effects of atorvastatin in I/R injury‑associated diseases.
authors.affiliation: Department of Nephrology, Huadu District People's Hospital, Southern Medical University, Guangzhou, Guangdong 510800, P.R. China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Li
authors.affiliation: Department of Nephrology, Huadu District People's Hospital, Southern Medical University, Guangzhou, Guangdong 510800, P.R. China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Su
authors.affiliation: Department of Nephrology, Huadu District People's Hospital, Southern Medical University, Guangzhou, Guangdong 510800, P.R. China.
authors.forename: Yun-Fang
authors.initials: YF
authors.lastname: Zhang
authors.affiliation: Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Huadu District People's Hospital, Southern Medical University, Guangzhou, Guangdong 510800, P.R. China.
authors.forename: Bao-Jun
authors.initials: BJ
authors.lastname: Hua
mesh_terms: D000818:Animals; D000069059:Atorvastatin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000096:biosynthesis; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000096:biosynthesis; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010100:Oxygen / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics*; D000067996:RAW 264.7 Cells; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D047495:PPAR gamma; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000069059:Atorvastatin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D005947:Glucose; D010100:Oxygen