| First Author | Long H | Year | 2019 |
| Journal | Neurochem Res | Volume | 44 |
| Issue | 8 | Pages | 1830-1839 |
| PubMed ID | 31134514 | Mgi Jnum | J:304709 |
| Mgi Id | MGI:6695864 | Doi | 10.1007/s11064-019-02817-1 |
| Citation | Long H, et al. (2019) TREM2 Attenuates Abeta1-42-Mediated Neuroinflammation in BV-2 Cells by Downregulating TLR Signaling. Neurochem Res 44(8):1830-1839 |
| abstractText | The pathogenesis of late-onset Alzheimer's disease (LOAD) mainly involves abnormal accumulation of extracellular beta-amyloid (Abeta) 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 Abeta 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 Abeta1-42 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, Abeta1-42 content, and expression of inflammatory markers (IL-1beta, IL-6, and TNF-alpha). TREM2 overexpression up-regulated cell activity, promoted clearance of Abeta1-42 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-1beta, TNF-alpha, and IL-6) in BV-2 cells overexpressing TREM2. In conclusion, TREM2 promoted clearance of Abeta1-42 by BV-2 cells and restored BV-2 cell viability from Abeta1-42-mediated neuroinflammation by downregulating TLRs. These findings suggest that TREM2 may be a target for LOAD therapy. |
