OBJECTIVE To investigate the role of triggering receptor expressed on myeloid cells-2(TREM2) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) model mice with Parkinson disease(PD) and explore the underlying s...OBJECTIVE To investigate the role of triggering receptor expressed on myeloid cells-2(TREM2) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) model mice with Parkinson disease(PD) and explore the underlying signaling pathway that mediate TREM2 function.METHODS TREM2 adenovirus were stereologically injected into the right striatum.Two weeks later,MPTP was intraperitoneally injected to produce the acute MPTP mouse model of PD.Mice were sacrificed at different time points following MPTP for biochemical or histological study.RESULTS Overexpression of TREM2 remarkably reduced MPTP-induced neuropathology including the dopaminergic neurodegeneration and neuroinflammation in vivo.Further study revealed that TREM2 may inhibit neuroinflammation by negatively regulating the TRAF6/TLR4-mediated activation of the MAPK and NF-κB signaling pathways.CONCLUSION TREM2 may have important neuroprotective effects against PD by critical y modulating neuroinflammatory responses.展开更多
目的观察血管活性肠肽（vasoactive intestinal peptide,VIP）对脂多糖（lipopolysaccharides,LPS）应激的小鼠成纤维细胞髓样细胞表达触发受体-2（TREM-2）表达的影响,并初步探讨其信号转导通路。方法利用LPS腹腔注射建立急性肺损伤（...目的观察血管活性肠肽（vasoactive intestinal peptide,VIP）对脂多糖（lipopolysaccharides,LPS）应激的小鼠成纤维细胞髓样细胞表达触发受体-2（TREM-2）表达的影响,并初步探讨其信号转导通路。方法利用LPS腹腔注射建立急性肺损伤（ALI）小鼠模型;采用VIP慢病毒气管滴注,q PCR检测肺组织TREM-2的表达。选用q PCR和流式细胞术检测VIP对LPS应激的小鼠成纤维细胞TREM-2表达的影响;并观察PKC信号通路阻断剂（H-7）、PKA信号通路阻断剂（H-89）、MAPK信号通路阻断剂（PD98059）和Ca M信号通路阻断剂（W-7）对VIP调控TREM-2表达的影响。结果 ALI时小鼠肺组织TREM-2 m RNA表达降低,而VIP可上调肺组织TREM-2 m RNA的表达。LPS下调小鼠成纤维细胞TREM-2 m RNA的表达,VIP可呈时间依赖性上调TREM-2 m RNA的表达（0、3、6、12和24 h）,且在6 h达到峰值;并呈剂量相关性上调TREM-2 m RNA的表达（10^（-10）、10^（-9）、10^（-8）和10^（-7）mol/L）,以10^（-8）mol/L作用最明显。VIP对LPS应激6 h增加小鼠成纤维细胞TREM-2 m RNA和蛋白表达的效应可被H-7、PD98059以及W-7所阻断。结论 LPS下调小鼠成纤维细胞TREM-2的表达,而VIP可上调LPS应激的小鼠成纤维细胞TREM-2 m RNA的表达,其胞内信号转导途径可能与PKC、MAPK及Ca M有关。展开更多
基金Shandong Province Science and Technology Program (2016GSF201061).
文摘OBJECTIVE To investigate the role of triggering receptor expressed on myeloid cells-2(TREM2) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) model mice with Parkinson disease(PD) and explore the underlying signaling pathway that mediate TREM2 function.METHODS TREM2 adenovirus were stereologically injected into the right striatum.Two weeks later,MPTP was intraperitoneally injected to produce the acute MPTP mouse model of PD.Mice were sacrificed at different time points following MPTP for biochemical or histological study.RESULTS Overexpression of TREM2 remarkably reduced MPTP-induced neuropathology including the dopaminergic neurodegeneration and neuroinflammation in vivo.Further study revealed that TREM2 may inhibit neuroinflammation by negatively regulating the TRAF6/TLR4-mediated activation of the MAPK and NF-κB signaling pathways.CONCLUSION TREM2 may have important neuroprotective effects against PD by critical y modulating neuroinflammatory responses.
文摘目的观察血管活性肠肽（vasoactive intestinal peptide,VIP）对脂多糖（lipopolysaccharides,LPS）应激的小鼠成纤维细胞髓样细胞表达触发受体-2（TREM-2）表达的影响,并初步探讨其信号转导通路。方法利用LPS腹腔注射建立急性肺损伤（ALI）小鼠模型;采用VIP慢病毒气管滴注,q PCR检测肺组织TREM-2的表达。选用q PCR和流式细胞术检测VIP对LPS应激的小鼠成纤维细胞TREM-2表达的影响;并观察PKC信号通路阻断剂（H-7）、PKA信号通路阻断剂（H-89）、MAPK信号通路阻断剂（PD98059）和Ca M信号通路阻断剂（W-7）对VIP调控TREM-2表达的影响。结果 ALI时小鼠肺组织TREM-2 m RNA表达降低,而VIP可上调肺组织TREM-2 m RNA的表达。LPS下调小鼠成纤维细胞TREM-2 m RNA的表达,VIP可呈时间依赖性上调TREM-2 m RNA的表达（0、3、6、12和24 h）,且在6 h达到峰值;并呈剂量相关性上调TREM-2 m RNA的表达（10^（-10）、10^（-9）、10^（-8）和10^（-7）mol/L）,以10^（-8）mol/L作用最明显。VIP对LPS应激6 h增加小鼠成纤维细胞TREM-2 m RNA和蛋白表达的效应可被H-7、PD98059以及W-7所阻断。结论 LPS下调小鼠成纤维细胞TREM-2的表达,而VIP可上调LPS应激的小鼠成纤维细胞TREM-2 m RNA的表达,其胞内信号转导途径可能与PKC、MAPK及Ca M有关。
