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,regula...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.展开更多
目的探讨阿尔茨海默病(Alzheimer′s disease,AD)患者血清中髓样细胞触发受体-1(triggering receptor expressed on myeloid cells-1,TREM-1)的表达水平及临床诊断价值。方法收集2021年1~6月就诊于江苏大学附属医院神经内科门诊的40例A...目的探讨阿尔茨海默病(Alzheimer′s disease,AD)患者血清中髓样细胞触发受体-1(triggering receptor expressed on myeloid cells-1,TREM-1)的表达水平及临床诊断价值。方法收集2021年1~6月就诊于江苏大学附属医院神经内科门诊的40例AD患者为AD组,另选取20例健康体检者为对照组。AD组和对照组在入组时采用ELISA试剂盒检测血清中TREM-1的浓度,采用MMSE量表评价患者的认知功能,分析血清TREM-1浓度与简易精神状态检查(mini-mental state examination,MMSE)量表评分的相关性,ROC曲线评价TREM-1对AD的诊断效能。结果AD组血清TREM-1浓度高于对照组;与MMSE呈负相关(r=-1.025,P<0.01);ROC曲线结果显示血清TREM-1曲线下面积为0.874(P<0.01),敏感度为75.0%,特异性为87.5%。结论AD患者血清中TREM-1表达升高,可作为AD诊断的生物学标志物。展开更多
基金supported by the National Natural Science Foundation of China,Nos.82271257(to YZ)and 82071228(to YZ)Qing Lan Project(to YZ)+1 种基金Open Competition Grant of Xuzhou Medical University(to YZ)Postgraduate Research&Practice Innovation Program of Jiangsu Province,No.KYCX21_2705(to TS)。
文摘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.
文摘目的探讨阿尔茨海默病(Alzheimer′s disease,AD)患者血清中髓样细胞触发受体-1(triggering receptor expressed on myeloid cells-1,TREM-1)的表达水平及临床诊断价值。方法收集2021年1~6月就诊于江苏大学附属医院神经内科门诊的40例AD患者为AD组,另选取20例健康体检者为对照组。AD组和对照组在入组时采用ELISA试剂盒检测血清中TREM-1的浓度,采用MMSE量表评价患者的认知功能,分析血清TREM-1浓度与简易精神状态检查(mini-mental state examination,MMSE)量表评分的相关性,ROC曲线评价TREM-1对AD的诊断效能。结果AD组血清TREM-1浓度高于对照组;与MMSE呈负相关(r=-1.025,P<0.01);ROC曲线结果显示血清TREM-1曲线下面积为0.874(P<0.01),敏感度为75.0%,特异性为87.5%。结论AD患者血清中TREM-1表达升高,可作为AD诊断的生物学标志物。
