Volume 29, Issue 3
DOI: 10.24205/03276716.2020.742
ApoE and TREM2 regulate LPS-induced inflammatory responses in a joint manner
Abstract
Alzheimer's disease (AD) has been considered as the most common reason of dementia in the people. AD is associated with TREM2 genetic variants, an innate immune receptor located in the brain's microglia. Apo lipoprotein E (ApoE) and (TREM2) are strongly expressed in microglia that control responses of inflammatory respectively in the central nervous system (CNS). Here we demonstrate that LPS (lipopolysaccharide) down-regulates the appearance of small type Trem2 and ApoE in primary microglia. In Trem2-/- and apoE-/- rats, primary microglia, we found that both ApoE and Trem2 can respectively regulate LPS-induced inflammatory cytokine release. Importantly, primary microglia of Trem2/ApoE double knockout mice was hypersensitive to LPS stimulation when compared with single gene knockout mice. It suggested that ApoE and TREM2 regulate LPS-induced inflammatory responses in a joint manner. Our data indicate that ApoE-TREM2 dealings in microglia that plays serious roles in modulating neuron inflammation, and establishes a crucial connection among two proteins whose genes are closely associated with the risk of AD.
Keywords
ApoE, TREM2, LPS, microglia, inflammation.