title: Metformin Inhibits Advanced Glycation End Products-Induced Inflammatory Response in Murine Macrophages Partly through AMPK Activation and RAGE/NFκB Pathway Suppression.
abstract: Advanced glycation end products (AGEs) are major inflammatory mediators in diabetes, affecting atherosclerosis progression via macrophages. Metformin slows diabetic atherosclerosis progression through mechanisms that remain to be fully elucidated. The present study of murine bone marrow derived macrophages showed that (1) AGEs enhanced proinflammatory cytokines (interleukin-1β(IL-1β), IL-6, and tumor necrosis factor-α(TNF-α)) mRNA expression, RAGE expression, and NFκB activation; (2) metformin pretreatment inhibited AGEs effects and AGEs-induced cluster designation 86 (CD86) (M1 marker) expression, while promoting CD206 (M2 marker) surface expression and anti-inflammatory cytokine (IL-10) mRNA expression; and (3) the AMPK inhibitor, Compound C, attenuated metformin effects. In conclusion, metformin inhibits AGEs-induced inflammatory response in murine macrophages partly through AMPK activation and RAGE/NFκB pathway suppression.
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China; Department of Cardiology, Central Hospital of Minhang District, 170 Xinsong Road, Shanghai 201199, China.
authors.forename: Zhong'e
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Cardiology, Central Hospital of Minhang District, 170 Xinsong Road, Shanghai 201199, China.
authors.forename: Xian
authors.identifier: 0000-0001-5535-0460
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Cardiology, Central Hospital of Minhang District, 170 Xinsong Road, Shanghai 201199, China.
authors.forename: Chengjun
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Central Hospital of Minhang District, 170 Xinsong Road, Shanghai 201199, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Chengxing
authors.identifier: 0000-0002-3882-7586
authors.initials: C
authors.lastname: Shen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000187:drug effects / Q000235:genetics; D017127:Glycation End Products, Advanced / Q000187:drug effects* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007249:Inflammation; D053583:Interleukin-1beta / Q000187:drug effects / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000235:genetics
chemical_list: C000593873:Ager protein, mouse; D016207:Cytokines; D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D008687:Metformin; D055372:AMP-Activated Protein Kinases