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TREM2 Attenuates Aβ1-42-Mediated Neuroinflammation in BV-2 Cells by Downregulating TLR Signaling

  • Huiping Long
  • Gang Zhong
  • Chengzhi Wang
  • Jian Zhang
  • Yueling Zhang
  • Jinglian Luo
  • Shengliang ShiEmail author
Original Paper

Abstract

The pathogenesis of late-onset Alzheimer's disease (LOAD) mainly involves abnormal accumulation of extracellular β-amyloid (Aβ) and the consequent neurotoxic effects. The triggering receptor expressed on myeloid cells 2 (TREM2) gene is associated with the pathogenesis of LOAD and plays important roles in mediating the phagocytosis of Aβ by microglia and regulating inflammation in central nervous system. However, the exact mechanisms of these processes have not yet been clarified. In this study, we investigated the mechanism by which TREM2 regulates neuroinflammation and promotes Aβ1-42 clearance by BV-2 cells and further elucidated the underlying molecular mechanisms. We either silenced or overexpressed TREM2 in BV-2 cells and evaluated the cell viability, Aβ1-42 content, and expression of inflammatory markers (IL-1β, IL-6, and TNF-α). TREM2 overexpression up-regulated cell activity, promoted clearance of Aβ1-42 by BV-2 cells, and down-regulated expression of the inflammatory factors. In addition, TREM2 overexpression downregulation the expression of the TLR family (TLR2, TLR4 and TLR6) in BV-2 cells. Moreover, LPS, as an agonist of the TLR family, up-regulated the expression of inflammatory cytokines (IL-1β, TNF-α, and IL-6) in BV-2 cells overexpressing TREM2. In conclusion, TREM2 promoted clearance of Aβ1-42 by BV-2 cells and restored BV-2 cell viability from Aβ1-42-mediated neuroinflammation by downregulating TLRs. These findings suggest that TREM2 may be a target for LOAD therapy.

Keywords

Alzheimer's disease TREM2 TLR signaling Neuroinflammation 

Notes

Acknowledgments

This work was supported by the Natural Science Foundation of China (Grant No. 81460183).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019
corrected publication 2019

Authors and Affiliations

  • Huiping Long
    • 1
  • Gang Zhong
    • 2
  • Chengzhi Wang
    • 3
  • Jian Zhang
    • 1
  • Yueling Zhang
    • 1
  • Jinglian Luo
    • 1
  • Shengliang Shi
    • 1
    Email author
  1. 1.Department of NeurologyThe Second Affiliated Hospital of Guangxi Medical UniversityNanningChina
  2. 2.Guangxi Medical UniversityNanningChina
  3. 3.Department of NeurologyThe Third Affiliated Hospital of Guangxi Medical UniversityNanningChina

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