title: Pioglitazone alleviates inflammation in diabetic mice fed a high-fat diet via inhibiting advanced glycation end-product-induced classical macrophage activation.
abstract: Classically activated macrophages (M1) are associated with inflammation in diabetic patients. Inflammation is a known risk factor in diabetes. The present study tested the hypothesis that pioglitazone (PIO) alleviates inflammation in diabetic mice fed a high-fat diet by inhibiting advanced glycation end-product (AGE)-induced classical macrophage activation. It was found that AGE treatment promoted the transcription of pro-inflammatory molecules and M1 surface markers, whereas PIO increased the expression of anti-inflammatory genes and decreased the expression of pro-inflammatory mediators in bone marrow-derived macrophages (BMDMs) in a dose-dependent manner. Furthermore, pretreatment with PIO abrogated the effects of AGE on pro-inflammatory markers and partly inhibited AGE-induced nuclear factor-κB (NF-κB) activation. PIO treatment partly reduced the inflammatory phenotype in diabetic ApoE(-/-) mice, and significantly reduced NF-κB activation in plaques. Therefore, we conclude that PIO blocks classical activation of macrophages and attenuates inflammation in mouse models of diabetes.
authors.affiliation: Department of Cardiology, Central Hospital of Minhang District, Shanghai, China.|Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Central Hospital of Minhang District, Shanghai, China.|Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Zhong'e
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Qingdao University, China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Ge
authors.affiliation: Department of Cardiology, Tongling People's Hospital, China.
authors.forename: Tongqing
authors.initials: T
authors.lastname: Yao
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Chengxing
authors.initials: C
authors.lastname: Shen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001853:Bone Marrow / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D059305:Diet, High-Fat; D017127:Glycation End Products, Advanced / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D016688:Mice, Inbred NOD; D016328:NF-kappa B / Q000235:genetics; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage*
chemical_list: D000893:Anti-Inflammatory Agents; D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D045162:Thiazolidinediones; D000077205:Pioglitazone
keywords: NF-κB; advanced glycation end-product; inflammation; macrophage polarization; pioglitazone