Abstract:

In the present study, we aimed to explore the anti-inflammatory mechanism of acetylcholine (ACh) and to provide further evidence for the investigation of the inflammatory pathogenesis of Alzheimer’s disease (AD) and its therapeutic drugs. The in vitro model of Aβ_25?35-induced inflammatory injury in microglial cell line BV-2 cells was established to observe the anti-inflammatory effect of ACh chloride. In the presence or absence of α7 nAChR blocker (α-bungarotoxin), the expressions of IL-1β and IL-1RA and their ratio after ACh treatment were evaluated by ELISA. The expression and phosphorylation levels of MAPK (JNK, p38, and ERK1/2) and NF-κB pathway molecules were determined by Western blot analysis or EMSA, respectively. The results showed that ACh could significantly reduce the ratio of IL-1β/IL-1RA, antagonize the inflammatory activity of the IL-1 system induced by Aβ_25?35, and restore the viability of BV-2 cells. Pretreatment with α7 nAChR blocker could block the inhibitory effect of ACh on the IL-1β/IL-1RA ratio. Meanwhile, α7 nAChR blocker could block the phosphorylation level of ERK1/2 MAPK protein and NF-κB activation downstream. Our study suggested that ACh could regulate IL-1 system inflammatory response induced by Aβ_25?35 in BV-2 cells and maintain IL-1 subfamily balance, which was mediated by α7 nAChR and involved ERK1/2 MAPK and NF-κB pathways. This study provided a basis for exploring AD inflammatory pathogenesis and also a reference for discovering new targets for AD treatment.

Key words: Acetylcholine, Interleukin-1β, IL-1 receptor antagonist, β-Amyloid protein, Alzheimer's disease