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Pioglitazone alleviates inflammation in diabetic mice fed a high‐fat diet via inhibiting advanced glycation end‐product‐induced classical macrophage activation
Author(s) -
Jin Xian,
Liu Liang,
Zhou Zhong'e,
Ge Junhua,
Yao Tongqing,
Shen Chengxing
Publication year - 2016
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13735
Subject(s) - inflammation , advanced glycation end product , pioglitazone , glycation , macrophage , diabetes mellitus , endocrinology , medicine , proinflammatory cytokine , immunology , type 2 diabetes , chemistry , biochemistry , in vitro
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 ( BMDM s) 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.