DOCK8干扰通过抑制STAT3/NLRP3/NF-κB信号减轻Aβ诱导的BV2细胞损伤

Abstract

Dementia is defined as memory loss and other cognitive decline and it severely influences daily life. Alzheimer's disease (AD) is the most common cause of dementia. Dedicator of cytokinesis 8 (DOCK8) is reported to be involved in neurological diseases. The present study focused on investigating the role that DOCK8 serves in AD and addressing its hidden regulatory mechanism. Initially, Aβ_1‑42 (Aβ) was applied for the administration of BV2 cells. Subsequently, the mRNA and protein expression levels of DOCK8 were evaluated utilizing reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting. After the DOCK8 silencing, immunofluorescence staining (IF), ELISA, wound healing and Transwell assays were applied to assess ionized calcium binding adapter molecule‑1 (IBA‑1) expression, release of inflammatory factors, migration and invasion in Aβ‑induced BV2 cells. IF was used to evaluate cluster of differentiation (CD)11b expression. RT‑qPCR and western blotting were to analyze the levels of M1 cell markers inducible nitric oxide synthase (iNOS) and CD86. The expression of STAT3/NLR family pyrin domain containing 3 (NLRP3)/NF‑κB signaling‑related proteins were determined by western blotting. Finally, the viability and apoptosis in hippocampal HT22 cells with DOCK8 depletion were estimated. Results revealed that Aβ induction greatly stimulated the expression levels of IBA‑1 and DOCK8. DOCK8 silencing suppressed Aβ‑induced inflammation, migration and invasion of BV2 cells. Additionally, DOCK8 deficiency conspicuously decreased the expression levels of CD11b, iNOS and CD86. The expression of phosphorylated (p‑)STAT3, NLRP3, ASC, caspase1 and p‑p65 was downregulated in Aβ‑induced BV2 cells after DOCK8 depletion. STAT3 activator Colivelin reversed the effects of DOCK8 knockdown on IBA‑1 expression, inflammation, migration, invasion and M1 cell polarization. In addition, the viability and apoptosis in hippocampal HT22 cells stimulated by neuroinflammatory rele