Abstract

Background: Alzheimer disease (AD) is one of the most frequent neurodegenerative disorders that results in the progressive loss of memory and severe impairments and death. The experimental results showed that the neuroinflammation involving microglia and cytokines, especially the neuritic plaques composed of aggregates of β-amyloid protein, also play a major risk in AD. Biglycan (BGN) is involved in the regulation of neuronal cell division that could induce the expression of proinflammatory factors. Furthermore, BGN also exerts effects on β-amyloid-induced microglial dysfunction and contributes to AD pathogenesis. However, the mechanisms underlying the regulatory role of BGN on β-amyloid-induced microglial activation remain unclear. This study intended to investigate whether BGN could promote β-amyloid induced microglial activation through TLRs in immortalized murine microglial (BV2) cells.
Methods: The levels of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) were detected by enzyme-linked immunosorbent assay (ELISA). The Cell Counting kit-8 (CCK8) assay was performed to detect cell viability. The expression level of a microglia marker (CD11b) was detected by immunofluorescence. The mRNA and protein expression levels of BGN and Toll-like receptor 2 (TLR2) were determined by quantitative RT-PCR and western blotting.
Results: BGN was upregulated in activated microglial cells. Knockdown of BGN efficiently attenuated β-amyloid-induced microglial activation and expressions of proinflammatory factors. Furthermore, the present findings provided evidence showing that BGN could regulate β-amyloid-induced microglial activation through TLR2 in BV2 cells.
Conclusions: Our results suggested that TLR2 signaling may be involved in the regulatory role of BGN in β-amyloid-induced microglial activation.

DOI: 10.7754/Clin.Lab.2020.200252