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标题:TREM2 promotes Aβ phagocytosis by upregulating C/EBPα-dependent CD36 expression in microglia.
时间:2020-01-14 22:21:42
DOI:10.1038/s41598-017-11634-x
PMID:28894284
作者:Su-Man Kim;Bo-Ram Mun;Sun-Jun Lee
出版源: Scientific Reports ,2017 ,7 (1) :11118
摘要:Natural killer (NK) cells have been well known to play a critical role in innate immunity, but they are also capable of regulating adaptive immunity through the induction of T cell-mediated memory response and B cell-mediated autoimmune response. NK cells are differentiated from hematopoietic stem cells (HSCs) in the bone marrow (BM), and a series of surface molecules are expressed on NK cells... [Show full abstract]
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目录:
  • TREM2 promotes Aβ phagocytosis by upregulating C/EBPα-dependent CD36 expression in microglia
    • Results
      • TREM2 TG mice showed enhanced learning and memory, whereas a defective tendency was observed in KO mice.
      • Aβ protein levels were increased in the brain of TREM2 KO mice.
      • The protective effect of TREM2 against Aβ-induced neurotoxicity.
      • TREM2 is required for the direct clearance of Aβ by microglia.
      • TREM2 enhanced the phagocytic efficiency of Aβ by inducing CD36 expression.
      • TREM2 increases the expression level of CD36 by upregulating C/EBPα in microglia.
    • Discussion
    • Methods
      • Generation of TREM2 Transgenic Mice.
      • Animals.
      • Culture of embryonic and neonatal neuronal cells and BV2 cells.
      • Culture of primary microglia.
      • Transfection of BV2 cells by electroporation and viral infection of primary microglia.
      • Aβ oligomerization and lactate dehydrogenase (LDH) release assay.
      • Immunofluorescence staining.
      • Semi-quantitative RT-PCR.
      • Western blot and flow cytometric analysis.
      • Phagocytosis and ex vivo brain slice assay.
      • Plasmid construction and promoter assay.
      • Rotarod and Morris water maze tests.
      • Statistical analysis.
    • Acknowledgements
    • Figure 1 Learning and memory was enhanced in TREM2 TG mice, but TREM2 KO mice showed a tendency toward defects.
    • Figure 2 Aβ protein levels were increased in KO mice.
    • Figure 3 TREM2 increased the viability of neuronal cells in the presence of Aβ.
    • Figure 4 Deficiency of TREM2 signaling impairs the phagocytic activity of microglia.
    • Figure 5 TREM2 promotes Aβ phagocytosis by upregulating CD36 in microglia.
    • Figure 6 TREM2-induced C/EBPα promotes the transcription of CD36 in microglia.

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