title: Advanced Glycation End Products Enhance Macrophages Polarization into M1 Phenotype through Activating RAGE/NF-κB Pathway.
abstract: Atherosclerotic lesions are accelerated in patients with diabetes. M1 (classically activated in contrast to M2 alternatively activated) macrophages play key roles in the progression of atherosclerosis. Since advanced glycation end products (AGEs) are major pathogenic factors and active inflammation inducers in diabetes mellitus, this study assessed the effects of AGEs on macrophage polarization. The present study showed that AGEs significantly promoted macrophages to express IL-6 and TNF-α. M1 macrophage markers such as iNOS and surface markers including CD11c and CD86 were significantly upregulated while M2 macrophage markers such as Arg1 and CD206 remained unchanged after AGEs stimulation. AGEs significantly increased RAGE expression in macrophages and activated NF-κB pathway, and the aforementioned effects were partly abolished by administration of anti-RAGE antibody or NF-κB inhibitor PDTC. In conclusion, our results suggest that AGEs enhance macrophage differentiation into proinflammatory M1 phenotype at least partly via RAGE/NF-κB pathway activation.
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong 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: Xian
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Tongqing
authors.initials: T
authors.lastname: Yao
authors.affiliation: 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, Zhongda Hospital Affiliated to Southeast University, 89 Dingjiaqiao Road, Nanjing 210009, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Central Hospital of Minhang District, 170 Xinsong Road, Shanghai 201199, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Chengxing
authors.initials: C
authors.lastname: Shen
mesh_terms: D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D017127:Glycation End Products, Advanced / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D017127:Glycation End Products, Advanced; D015850:Interleukin-6; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha