巨噬细胞极化
化学
炎症
促炎细胞因子
下调和上调
M2巨噬细胞
细胞生物学
巨噬细胞
癌症研究
免疫学
体外
生物化学
生物
基因
作者
Jinxin Che,Dan Li,Wenxiang Hong,Longling Wang,Yu Guo,Mingxi Wu,Jialiang Lu,Lexian Tong,Qinjie Weng,Jiajia Wang,Xiaowu Dong
标识
DOI:10.1016/j.ejmech.2022.114732
摘要
The M2 polarized macrophages modulation has been described as a beneficial approach to facilitate the myelin repairing and inflammation microenvironment remodeling of multiple sclerosis (MS). Whereas, the M2 polarization involves complex mechanisms, and the modulators are still limited. As a protein kinase B (Akt) inhibitor, compound 2 was found promoting M2 polarization activity in our previous research, here we report the identification of a new modulator B9 with high M2-marker Arg1 upregulation activity, M1 polarization inhibition and ablated Akt1 inhibition activities. B9 has promising pharmacokinetic profiles, and significantly ameliorates the symptom and reduces demyelination in EAE mice. Moreover, the inflammation microenvironment is remodeled after B9 administration, with promoted M2-type macrophages and inhibited M1 polarization in the CNS and periphery, and suppressed the proinflammatory Th1 and Th17 cells responses. Therefore, the new macrophage M2 polarization modulator B9 could present a candidate for fulfilling the therapeutic strategies of MS.
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