Activating α7 nicotinic acetylcholine receptor inhibits NLRP3 inflammasome through regulation of β-arrestin-1.

摘要: Aims To evaluate whether activating α7 nicotinic acetylcholine receptor (α7nAChR) could inhibit the NOD-like family, pyrin domain containing 3 (NLRP3) inflammasome through regulation of β-arrestin-1 in monocyte/macrophage system, thus contributing to control neuroinflammation. Methods The protein levels NLRP3, caspase-1 (Casp-1) p20 and proCasp-1, interleukin-1β (IL-1β) p17 proIL-1β, IL-18 proIL-18 were measured using Western blotting. mRNA Casp-1 IL-1β detected by real-time PCR (RT-PCR). colocalization interaction NLRP3 immunofluorescence staining immunoprecipitation. Results expression was significantly increased colocalized with CD45-positive cells spinal cord experimental auto-immune encephalomyelitis (EAE) mice when compared sham mice, which attenuated pretreatment PNU282987, a specific α7nAChR agonist. PNU282987 also inhibited activation decreased production both lipopolysaccharide (LPS)/ATP-stimulated BV2 microglia vitro from EAE vivo, while inverse effects observed knockout mice. Furthermore, overexpression inhibitory effect on LPS/ATP-stimulated microglia. between vitro. Conclusions present study demonstrates that can lead inhibition via monocyte/microglia system.