TREM-1 mediates interaction between substantia nigra microglia and peripheral neutrophils  

作　　者：Tong Shen Guiyun Cui Hao Chen Long Huang Wei Song Jie Zu Wei Zhang Chuanying Xu Liguo Dong Yongmei Zhang 

机构地区：[1]Jiangsu Province Key Laboratory of Anesthesiology,Xuzhou Medical University,Xuzhou,Jiangsu Province,China [2]Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology,Xuzhou Medical University,Xuzhou,Jiangsu Province,China [3]NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs,Xuzhou,Jiangsu Province,China [4]Department of Neurology,The Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu Province,China

出　　处：《Neural Regeneration Research》2024年第6期1375-1384,共10页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,Nos.82271257(to YZ)and 82071228(to YZ);Qing Lan Project(to YZ);Open Competition Grant of Xuzhou Medical University(to YZ);Postgraduate Research&Practice Innovation Program of Jiangsu Province,No.KYCX21_2705(to TS)。

摘　　要：Microglia-mediated neuroinflammation is considered a pathological feature of Parkinson's disease.Triggering receptor expressed on myeloid cell-1(TREM-1)can amplify the inherent immune response,and crucially,regulate inflammation.In this study,we found marked elevation of serum soluble TREM-1 in patients with Parkinson's disease that positively correlated with Parkinson's disease severity and dyskinesia.In a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease,we found that microglial TREM-1 expression also increased in the substantia nigra.Further,TREM-1 knockout alleviated dyskinesia in a mouse model of Parkinson's disease and reduced dopaminergic neuronal injury.Meanwhile,TREM-1 knockout attenuated the neuroinflammatory response,dopaminergic neuronal injury,and neutrophil migration.Next,we established an in vitro 1-methyl-4-phenyl-pyridine-induced BV2 microglia model of Parkinson's disease and treated the cells with the TREM-1 inhibitory peptide LP17.We found that LP17 treatment reduced apoptosis of dopaminergic neurons and neutrophil migration.Moreover,inhibition of neutrophil TREM-1 activation diminished dopaminergic neuronal apoptosis induced by lipopolysaccharide.TREM-1 can activate the downstream CARD9/NF-κB proinflammatory pathway via interaction with SYK.These findings suggest that TREM-1 may play a key role in mediating the damage to dopaminergic neurons in Parkinson's disease by regulating the interaction between microglia and peripheral neutrophils.

关 键 词：1-methyl-4-phenylpyridiniumion dopaminergic neurons infiltration 1-methyl-4-phenyl-1 2 3 6-TETRAHYDROPYRIDINE MICROGLIA NEUTROPHILS neuroinflammation Parkinson's disease SYK TREM-1 

分 类 号：R742.5[医药卫生—神经病学与精神病学]