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A20 保护脂多糖诱导的小胶质细胞外泌体刺激的神经元细胞凋亡。

A20 protects neuronal apoptosis stimulated by lipopolysaccharide-induced microglial exosomes.

机构信息

Department of Orthopedics, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.

Medical School of Nantong University, Nantong, Jiangsu Province, 226001, China; Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong, 226001, Jiangsu, China.

出版信息

Neurosci Lett. 2019 Nov 1;712:134480. doi: 10.1016/j.neulet.2019.134480. Epub 2019 Sep 4.

DOI:10.1016/j.neulet.2019.134480
PMID:31493550
Abstract

LPS-induced microglial activation has a major influence on neuronal damage in the inflammatory process. Integral to this is the cellular and molecular interaction between microglia and neurons. Exosomes, a mediator of communication between cells, can transfer lipids, proteins and nucleic acids, affecting many donor and recipient cells. To investigate the mechanism by which microglial exosomes regulate neuronal inflammation after traumatic brain injury, this study primarily analyzed the effect of microglial exosomes on neuronal apoptosis. Exosomes derived from lipopolysaccharide (LPS)-activated microglial cultures were identified and purified. Neurons treated with these exosomes underwent apoptosis. A20 (also known as TNF-inducible protein 3, TNFAIP3) is a deubiquitinating enzyme with key anti-inflammatory functions. A20 is of huge significance to the degeneration and development of neuron. Importantly, A20 protects the exosomes-induced neuronal death, while A20 knockdown increases neuronal death. This study shows that exosomes may be critical for communication between microglia and neurons.

摘要

脂多糖诱导的小胶质细胞激活对炎症过程中的神经元损伤有重大影响。这其中的关键是小胶质细胞和神经元之间的细胞和分子相互作用。外泌体是细胞间通讯的介质,可以传递脂质、蛋白质和核酸,影响许多供体细胞和受体细胞。为了研究小胶质细胞外泌体在创伤性脑损伤后调节神经元炎症的机制,本研究主要分析了小胶质细胞外泌体对神经元凋亡的影响。鉴定并纯化了脂多糖(LPS)激活的小胶质细胞培养物衍生的外泌体。用这些外泌体处理的神经元发生了凋亡。A20(也称为 TNF 诱导蛋白 3,TNFAIP3)是一种具有关键抗炎功能的去泛素化酶。A20 对神经元的变性和发育具有重要意义。重要的是,A20 可以保护外泌体诱导的神经元死亡,而 A20 的敲低则会增加神经元死亡。本研究表明,外泌体可能是小胶质细胞和神经元之间通讯的关键。

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