ACSL4 通过调节脂质代谢和 VGLL4 表达促进小胶质细胞介导的神经炎症。

ACSL4 promotes microglia-mediated neuroinflammation by regulating lipid metabolism and VGLL4 expression.

机构信息

Institute of Neuroregeneration and Neurorehabilitation, Qingdao University, Ningxia Road 308, Qingdao 266071, Shandong, China; Qingdao Medical College, Qingdao University, Qingdao 266071, China.

Department of Interventional Radiology, The Affiliated Hospital of Qingdao University, Jiangsu Road 16, Qingdao 266000, Shandong, China.

出版信息

Brain Behav Immun. 2023 Mar;109:331-343. doi: 10.1016/j.bbi.2023.02.012. Epub 2023 Feb 14.

DOI:10.1016/j.bbi.2023.02.012

PMID:36791893

Abstract

Acyl-CoA synthetase long-chain family member 4 (ACSL4) is an important isozyme in polyunsaturated fatty acid (PUFA) metabolism. The role of ACSL4 in the lipopolysaccharide (LPS)-induced inflammation of microglia, and the effects of ACSL4-mediated inflammation on the progression of Parkinson's disease (PD) are unknown. In this study, we found that ACSL4 expression was increased after LPS stimulation. Knocking down ACSL4 in microglia decreased proinflammatory cytokine production. Mechanistically, ACSL4 reduced vestigial-like family member 4(VGLL4) expression to promote NF-κB signal transduction; and ACSL4 regulated lipid composition after LPS stimulation. In addition, knocking down ACSL4 alleviated neuroinflammation in a systemic LPS model and acute l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) model. These data revealed ACSL4 to be a novel regulator that promotes microglia-mediated neuroinflammation by regulating VGLL4 expression and lipid metabolism.

摘要

酰基辅酶 A 合成酶长链家族成员 4（ACSL4）是多不饱和脂肪酸（PUFA）代谢中的重要同工酶。ACSL4 在脂多糖（LPS）诱导的小胶质细胞炎症中的作用以及 ACSL4 介导的炎症对帕金森病（PD）进展的影响尚不清楚。在这项研究中，我们发现 LPS 刺激后 ACSL4 的表达增加。在小胶质细胞中敲低 ACSL4 会减少促炎细胞因子的产生。在机制上，ACSL4 通过降低小脚蛋白样家族成员 4（VGLL4）的表达来促进 NF-κB 信号转导；并且 ACSL4 在 LPS 刺激后调节脂质组成。此外，敲低 ACSL4 可减轻全身 LPS 模型和急性 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）模型中的神经炎症。这些数据表明，ACSL4 通过调节 VGLL4 表达和脂质代谢，成为一种促进小胶质细胞介导的神经炎症的新型调节剂。