PMID- 32093892
OWN - NLM
STAT- MEDLINE
DCOM- 20201109
LR  - 20201109
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 525
IP  - 2
DP  - 2020 Apr 30
TI  - Advanced glycation end products enhance M1 macrophage polarization by activating 
      the MAPK pathway.
PG  - 334-340
LID - S0006-291X(20)30321-1 [pii]
LID - 10.1016/j.bbrc.2020.02.053 [doi]
AB  - BACKGROUND: beta-cell dysfunction is one of the core pathogenetic mechanisms of type 
      2 diabetes mellitus (T2DM). However, there are currently no effective therapeutic 
      strategies to preserve beta-cell mass and function. The role of islet macrophage 
      phenotype reprogramming in beta-cell dysfunction has attracted great attention. 
      Given that advanced glycation end products (AGEs) are major pathogenic factors in 
      T2DM, we investigated the effect of AGEs on macrophage activation and their role 
      in beta-cell dysfunction. METHODS: We examined cytokine secretion, M1 and M2 
      macrophage-associated marker expression and MAPK phosphorylation levels in 
      AGEs-stimulated macrophages. MIN6 cells were cocultured with AGEs-pretreated 
      macrophages to study the effect of AGEs-induced macrophage activation on beta-cell 
      dysfunction. RESULTS: We found that AGEs treatment significantly enhanced 
      macrophage secretion of proinflammatory cytokines. The expression of M1 
      macrophage markers, such as iNOS and the surface marker CD11c, was significantly 
      upregulated, whereas the expression of M2 macrophage markers, such as Arg1 and 
      CD206, was reciprocally downregulated upon AGEs stimulation. AGEs treatment 
      predominantly activated the MAPK pathway, and the inhibition of the MAPK pathway 
      partially attenuated the AGEs-induced polarization of macrophages. In addition, 
      coculture with AGEs-pretreated macrophages significantly inhibited the expression 
      of molecules involved in beta-cell function and was accompanied by the impairment of 
      glucose-stimulated insulin secretion (GSIS) in MIN6 cells. CONCLUSION: AGEs 
      enhance the expression of proinflammatory molecules by activating the MAPK 
      pathway. Moreover, these data imply that AGEs induce macrophage M1 phenotype 
      polarization but restrain M2 polarization, which might contribute to beta-cell 
      dysfunction in the pathogenesis of T2DM.
CI  - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - He, Sunyue
AU  - He S
AD  - Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai 
      Jiaotong University, 1665 Kongjiang Road, Shanghai, 200092, China.
FAU - Hu, Qiuyue
AU  - Hu Q
AD  - Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai 
      Jiaotong University, 1665 Kongjiang Road, Shanghai, 200092, China.
FAU - Xu, Xiaoyuan
AU  - Xu X
AD  - Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai 
      Jiaotong University, 1665 Kongjiang Road, Shanghai, 200092, China.
FAU - Niu, Yixin
AU  - Niu Y
AD  - Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai 
      Jiaotong University, 1665 Kongjiang Road, Shanghai, 200092, China.
FAU - Chen, Youming
AU  - Chen Y
AD  - Department of Cardiology, Xinhua Hospital, School of Medicine, Jiao Tong 
      University, 1665 Kongjiang Road, Shanghai, 200092, China.
FAU - Lu, Yao
AU  - Lu Y
AD  - Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai 
      Jiaotong University, 1665 Kongjiang Road, Shanghai, 200092, China.
FAU - Su, Qing
AU  - Su Q
AD  - Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai 
      Jiaotong University, 1665 Kongjiang Road, Shanghai, 200092, China. Electronic 
      address: suqingxinhua@163.com.
FAU - Qin, Li
AU  - Qin L
AD  - Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai 
      Jiaotong University, 1665 Kongjiang Road, Shanghai, 200092, China; Department of 
      Endocrinology, Xinhua Hospital Chongming Branch, School of Medicine, Shanghai 
      Jiaotong University, 25 Nanmen Road, Shanghai, 202150, China. Electronic address: 
      qinli@xinhuamed.com.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200221
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Cytokines)
RN  - 0 (Glycation End Products, Advanced)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Coculture Techniques
MH  - Cytokines/metabolism
MH  - Diabetes Mellitus, Type 2/etiology/pathology
MH  - Glycation End Products, Advanced/*pharmacology
MH  - Insulin-Secreting Cells/metabolism/pathology
MH  - MAP Kinase Signaling System/drug effects
MH  - Macrophage Activation/*drug effects
MH  - Macrophages/drug effects/immunology/*metabolism
MH  - Mice
OTO - NOTNLM
OT  - AGEs
OT  - MAPK
OT  - Macrophage polarization
OT  - T2DM
OT  - beta-Cell dysfunction
COIS- Declaration of competing interests The authors declare that they have no conflict 
      of interest.
EDAT- 2020/02/26 06:00
MHDA- 2020/11/11 06:00
CRDT- 2020/02/26 06:00
PHST- 2019/11/19 00:00 [received]
PHST- 2020/02/07 00:00 [accepted]
PHST- 2020/02/26 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
PHST- 2020/02/26 06:00 [entrez]
AID - S0006-291X(20)30321-1 [pii]
AID - 10.1016/j.bbrc.2020.02.053 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2020 Apr 30;525(2):334-340. doi: 
      10.1016/j.bbrc.2020.02.053. Epub 2020 Feb 21.