Liu Etta Y L, Xia Yingjie, Kong Xiangpeng, Guo Maggie S S, Yu Anna X D, Zheng Brody Z Y, Mak Shinghung, Xu Miranda L, Tsim Karl W K
Key Laboratory of Food Quality and Safety of Guangdong Province, College of Food Science, South China Agricultural University, Guangzhou 510642, China.
Shenzhen Key Laboratory of Edible and Medicinal Bioresources, the Hong Kong University of Science and Technology, Shenzhen 518057, China.
Acta Pharm Sin B. 2020 Oct;10(10):1926-1942. doi: 10.1016/j.apsb.2020.05.005. Epub 2020 May 29.
Acetylcholine (ACh) regulates inflammation 7 nicotinic acetylcholine receptor (7 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-B onto the 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 7 nAChR and AChE was found in macrophages, suggesting the potential interaction of 7 nAChR and AChE. Besides, immunoprecipitation showed a close association of 7 nAChR and AChE protein in cell membrane. Hence, the novel function of AChE in macrophage by interacting with 7 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.
乙酰胆碱（ACh）通过7型烟碱型乙酰胆碱受体（7 nAChR）调节炎症。乙酰胆碱酯酶（AChE）是一种水解ACh的酶，在免疫细胞中表达，提示其在炎症反应中具有非经典功能。在此，在巨噬细胞表面鉴定出了与PRiMA相关的G4 AChE的表达。在脂多糖诱导的炎症过程中，NF-κB与启动子结合使AChE上调。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AChE抑制剂的情况相反。采用无酶活性的DNA构建体AChEmt来确定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。在巨噬细胞中发现了7 nAChR和AChE的共定位，提示7 nAChR与AChE之间可能存在相互作用。此外，免疫沉淀显示细胞膜中7 nAChR与AChE蛋白密切相关。因此，确定了AChE通过与7 nAChR相互作用在巨噬细胞中的新功能。除了水解ACh外，AChE在炎症反应调节中起直接作用。因此，AChE可作为通过抗炎反应治疗与年龄相关疾病的新靶点。
