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Interacting with α7 nAChR is a new mechanism for AChE to enhance the inflammatory response in macrophages
Acta Pharmaceutica Sinica B ( IF 14.5 ) Pub Date : 2020-05-29 , DOI: 10.1016/j.apsb.2020.05.005
Etta Y.L. Liu , Yingjie Xia , Xiangpeng Kong , Maggie S.S. Guo , Anna X.D. Yu , Brody Z.Y. Zheng , Shinghung Mak , Miranda L. Xu , Karl W.K. Tsim

Acetylcholine (ACh) regulates inflammation via α7 nicotinic acetylcholine receptor (α7 nAChR). Acetylcholinesterase (AChE), an enzyme hydrolyzing ACh, is expressed in immune cells suggesting non-classical function in inflammatory responses. Here, the expression of PRiMA-linked G4 AChE was identified on the surface of macrophages. In lipopolysaccharide-induced inflammatory processes, AChE was upregulated by the binding of NF-κB onto the ACHE promotor. Conversely, the overexpression of G4 AChE inhibited ACh-suppressed cytokine release and cell migration, which was in contrast to that of applied AChE inhibitors. AChEmt, a DNA construct without enzymatic activity, was adopted to identify the protein role of AChE in immune system. Overexpression of G4 AChEmt induced cell migration and inhibited ACh-suppressed cell migration. The co-localization of α7 nAChR and AChE was found in macrophages, suggesting the potential interaction of α7 nAChR and AChE. Besides, immunoprecipitation showed a close association of α7 nAChR and AChE protein in cell membrane. Hence, the novel function of AChE in macrophage by interacting with α7 nAChR was determined. Together with hydrolysis of ACh, AChE plays a direct role in the regulation of inflammatory response. As such, AChE could serve as a novel target to treat age-related diseases by anti-inflammatory responses.



中文翻译:

与之交互α 7的nAChR为乙酰胆碱酯酶的新机制以增强巨噬细胞的炎症反应

乙酰胆碱(ACh)规定炎症经由α -7烟碱乙酰胆碱受体(α 7的nAChR)。乙酰胆碱酯酶(AChE)是一种水解ACh的酶,在免疫细胞中表达,提示在炎症反应中具有非经典功能。在此,在巨噬细胞的表面鉴定出PRiMA连接的G4 AChE的表达。在脂多糖诱导的炎性过程,乙酰胆碱酯酶是由NF-κB的结合上调κ乙到ACHE启动子。相反,G4 AChE的过表达抑制了ACh抑制的细胞因子释放和细胞迁移,这与应用的AChE抑制剂相反。采用AChEmt,一种无酶活性的DNA构建体,来鉴定AChE在免疫系统中的蛋白质作用。G4 AChEmt的过表达诱导细胞迁移并抑制ACh抑制的细胞迁移。的共定位α 7的nAChR及AChE的巨噬细胞中被发现,表明的潜在相互作用α 7的nAChR与AChE。此外,免疫沉淀表明的紧密关联α 7的nAChR与AChE蛋白在细胞膜。因此,通过与α相互作用,AChE在巨噬细胞中的新功能测定了7 nAChR。与ACh水解一起,AChE在调节炎症反应中起直接作用。这样,AChE可以作为抗炎反应治疗年龄相关疾病的新靶标。

更新日期:2020-05-29
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