HMGB1 Facilitated Macrophage Reprogramming towards a Proinflammatory M1-like Phenotype in Experimental Autoimmune Myocarditis Development.
HMGB1 Facilitated Macrophage Reprogramming towards a Proinflammatory M1-like Phenotype in Experimental Autoimmune Myocarditis Development.
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实验性自身免疫性心肌炎发展中 HMGB1 促进巨噬细胞重编程为促炎性 M1 样表型
DOI：
10.1038/srep21884
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发表时间：
2016-02-22
影响因子：
4.6
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Su Z;Zhang P;Yu Y;Lu H;Liu Y;Ni P;Su X;Wang D;Liu Y;Wang J;Shen H;Xu W;Xu H
巨噬细胞可以是重编程的，如经典的活化巨噬细胞，M1或替代活化巨噬细胞，M2表型遵循环境危险信号，特别是炎症因子。巨噬细胞重编程现在被认为是疾病发展和/或消退的关键决定因素。实验性自身免疫性心肌炎（EAM）以单核/巨噬细胞浸润、Th 17细胞活化和高迁移率族蛋白1（HMGB 1）等炎性因子产生为特征。EAM中浸润的巨噬细胞是否可以重编程？HMGB 1与巨噬细胞重编程有关？我们的研究结果清楚地表明，在EAM中，浸润的巨噬细胞通过单核细胞/巨噬细胞耗竭或HMGB 1阻断而向促炎性M1样表型重编程和心脏保护;在体外，HMGB 1促进巨噬细胞向M1样表型重编程依赖于TLR 4-PI 3 K γ-Erk 1/2通路;此外，重编程的M1样巨噬细胞促进Th 17扩增。因此，我们推测HMGB 1除了直接调节Th 17细胞扩增外，还通过促进巨噬细胞向M1样表型重编程来促进EAM的发展。
Macrophages can be reprogramming, such as the classical activated macrophage, M1 or alternative activated macrophages, M2 phenotype following the milieu danger signals, especially inflammatory factors. Macrophage reprogramming is now considered as a key determinant of disease development and/or regression. Experimental autoimmune myocarditis (EAM) is characterized by monocytes/macrophage infiltration, Th17 cells activation and inflammatory factors producing such as high mobility group box 1 (HMGB1). Whether infiltrated macrophages could be reprogramming in EAM? HMGB1 was associated with macrophage reprogramming? Our results clearly demonstrated that infiltrated macrophage was reprogrammed towards a proinflammatory M1-like phenotype and cardiac protection by monocytes/macrophages depletion or HMGB1 blockade in EAM; in vitro, HMGB1 facilitated macrophage reprogramming towards M1-like phenotype dependent on TLR4-PI3Kγ-Erk1/2 pathway; furthermore, the reprogramming M1-like macrophage promoted Th17 expansion. Therefore, we speculated that HMGB1 contributed EAM development via facilitating macrophage reprogramming towards M1-like phenotype except for directly modulating Th17 cells expansion.