Advanced Glycation End Products Enhance M1 Macrophage Polarization by Activating the MAPK Pathway

2019 ◽  
Author(s):  
Sunyue He ◽  
Qiuyue Hu ◽  
Xiaoyuan Xu ◽  
Yixin Niu ◽  
Youming Chen ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Mapk Pathway ◽  
Macrophage Polarization ◽  
Advanced Glycation ◽  
M1 Macrophage ◽  
Glycation End Products ◽  
End Products

scholarly journals Advanced Glycation End Products Enhance Macrophages Polarization into M1 Phenotype through Activating RAGE/NF-κB Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Xian Jin ◽  
Tongqing Yao ◽  
Zhong’e Zhou ◽  
Jian Zhu ◽  
Song Zhang ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Advanced Glycation ◽  
Alternatively Activated Macrophages ◽  
M1 Macrophage ◽  
Glycation End Products ◽  
End Products ◽  
Patients With Diabetes ◽  
M1 Phenotype

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.

Abstract 268: Advanced Glycation End Products Effect on the Polarization of Macrophages Cardiac After Acute Myocardial Infarction in Wistar Rats

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Juliana O Rangel ◽  
Bianca Fracasso ◽  
Amanda Phaelante ◽  
Fernanda Curuja ◽  
Daniel Sturza ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Cardiac Remodeling ◽  
Wistar Rats ◽  
Macrophage Polarization ◽  
Tissue Homogenate ◽  
Advanced Glycation ◽  
M1 Macrophages ◽  
Glycation End Products ◽  
End Products

Macrophage phenotypes play an important role in post-MI cardiac remodeling. M1 macrophages have a proinflammatory phenotype and are found in the heart early after MI whereas M2 macrophages arise after and replace M1 macrophages in order to mediate the resolution of inflammation and angiogenesis. Advanced glycation end products (AGE) may modulate macrophage polarization but its functional role in the context of post-MI remains incompletely understood. Our goal is to assess whether AGE can polarize macrophages in post-MI and interfere in cardiac remodeling. We have collected experimental data from 68 male Wistar rats (2-3 month-old) divided in 4 groups: sham, MI + 0.9% NaCl (i.p.), MI + methylglyoxal (AGE inducer, 17 mg/kg/day; i.p.); and MI + aminoguanidine (anti-AGE agent, 0.5 g/L in drinking water). Subgroups were euthanized on days 2, 6, and 10 days post-MI. The echocardiographic analysis did not show differences in ejection fraction or akinetic/hypokinetic area among the MI groups. Cytokine levels were assessed by multiplex analysis in cardiac tissue homogenate. There was an increase of proinflammatory cytokine IL-6 on 10th day after surgery in MI group at the remote area, while IL-1β and IL-12 showed reduction compared with the sham group. Anti-inflammatory cytokine IL-10 did not show any difference among the groups. Until now, it is not possible to conclude whether AGE can induce macrophage polarization in vivo. More analyses are necessary to respond our objective.

scholarly journals Advanced Glycation End Products Impair Glucose-Stimulated Insulin Secretion of a Pancreaticβ-Cell Line INS-1-3 by Disturbance of Microtubule Cytoskeleton via p38/MAPK Activation

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Jia You ◽  
Zai Wang ◽  
Shiqing Xu ◽  
Wenjian Zhang ◽  
Qing Fang ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
P38 Mapk ◽  
Advanced Glycation End Products ◽  
Cell Model ◽  
Mapk Pathway ◽  
High Sensitivity ◽  
Advanced Glycation ◽  
Microtubule Depolymerization ◽  
Glycation End Products ◽  
End Products

Advanced glycation end products (AGEs) are believed to be involved in diverse complications of diabetes mellitus. Overexposure to AGEs of pancreaticβ-cells leads to decreased insulin secretion and cell apoptosis. Here, to understand the cytotoxicity of AGEs to pancreaticβ-cells, we used INS-1-3 cells as aβ-cell model to address this question, which was a subclone of INS-1 cells and exhibited high level of insulin expression and high sensitivity to glucose stimulation. Exposed to large dose of AGEs, even though more insulin was synthesized, its secretion was significantly reduced from INS-1-3 cells. Further, AGEs treatment led to a time-dependent increase of depolymerized microtubules, which was accompanied by an increase of activated p38/MAPK in INS-1-3 cells. Pharmacological inhibition of p38/MAPK by SB202190 reversed microtubule depolymerization to a stabilized polymerization status but could not rescue the reduction of insulin release caused by AGEs. Taken together, these results suggest a novel role of AGEs-induced impairment of insulin secretion, which is partially due to a disturbance of microtubule dynamics that resulted from an activation of the p38/MAPK pathway.

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