TREM2 Attenuates Aβ1-42-Mediated Neuroinflammation in BV-2 Cells by Downregulating TLR Signaling
| Autor: | Gang Zhong, Yueling Zhang, Huiping Long, Jian Zhang, Shengliang Shi, Chengzhi Wang, Jinglian Luo |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cell Survival Interleukin-1beta Down-Regulation Inflammation Biochemistry Proinflammatory cytokine Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Phagocytosis Downregulation and upregulation Alzheimer Disease medicine Animals Viability assay Receptors Immunologic Neuroinflammation Cell Line Transformed Amyloid beta-Peptides Membrane Glycoproteins Microglia Interleukin-6 Tumor Necrosis Factor-alpha Chemistry Toll-Like Receptors General Medicine Peptide Fragments Cell biology TLR2 030104 developmental biology medicine.anatomical_structure TLR4 medicine.symptom 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Neurochemical Research. 44:1830-1839 |
| ISSN: | 1573-6903 0364-3190 |
| DOI: | 10.1007/s11064-019-02817-1 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink