Triggering Receptor Expressed on Myeloid Cells 2 Overexpression Inhibits Proinflammatory Cytokines in Lipopolysaccharide-Stimulated Microglia

Abstract

Microglia play an important role in mediating inflammatory processes in the central nervous system (CNS). Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglia-specific receptor and could decrease neuropathology in Alzheimer's disease (AD). However, the detailed mechanism remains unclear. This study was designed to elucidate the effect of TREM2 on microglia. We showed that lipopolysaccharide (LPS) stimulation significantly increases proinflammatory cytokines and suppressed TREM2 in microglia. In addition, TREM2 overexpression inhibited LPS-induced microglia activation and elevated M2 phenotype of microglia. Together, our results demonstrate that TREM2 overexpression reduced LPS-induced proinflammatory cytokine release in microglia and increased M2 phenotype of microglia. These findings provide novel insights that the regulation of microglia polarization may be an approach for ameliorating microglia inflammation in neurodegenerative diseases.

Age and Sex Influence the Neuro-inflammatory Response to a Peripheral Acute LPS Challenge

“…Previous findings showed that LPS stimulation suppressed TREM2 levels in microglia, at the same time inducing pro-inflammatory cytokines secretion (Zheng et al, 2016). Peripheral LPS challenge (at a similar dose to that used in our study) induced up-regulation of TREML2 and down-regulation of TREM2 levels in microglia, and increase of pro-inflammatory cytokines (Zheng et al, 2016; Zhang et al, 2017). In particular, reduction of TREM2 was associated with a decreased microglia proliferation, an effect that was absent when TREML2 was knocked down.…”

DHA modulates MANF and TREM2 abundance, enhances neurogenesis, reduces infarct size, and improves neurological function after experimental ischemic stroke

“…showing that TREM2 is a proinflammatory mediator and an inhibitor of phagocytic microglial activity. 38,39 Depletion of microglial TREM2…”

TREML4 Promotes Inflammatory Programs in Human and Murine Macrophages and Alters Atherosclerosis Lesion Composition in the Apolipoprotein E Deficient Mouse

“…Similarly, TREM2 is expressed in a specific macrophage subset in diseased aortas, which have been ascribed to lipid metabolism functions (20). Additionally, TREM2 dampens TLR signaling in several myeloid cell types (21,22), controls macrophage and microglia function (23,24) and directly binds apolipoprotein E and other atherogenic lipids (25)(26)(27). In fact, multiple members of the TREM family have been shown to exhibit lipid binding properties (28) which makes this family a remarkable target for modulating the intertwined relationship between lipid signaling and inflammation.…”