科研之友
微信
新浪微博
Facebook
分享链接
摘要
AimsTo evaluate whether activating 7 nicotinic acetylcholine receptor (7nAChR) could inhibit the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome through regulation of -arrestin-1 in monocyte/macrophage system, thus contributing to the control of neuroinflammation. MethodsThe protein levels of NLRP3, caspase-1 (Casp-1) p20 and proCasp-1, interleukin-1 (IL-1) p17 and proIL-1, IL-18 and proIL-18 were measured using Western blotting. The mRNA levels of Casp-1 and IL-1 were detected by real-time PCR (RT-PCR). The colocalization and interaction of NLRP3 protein and -arrestin-1 were measured by immunofluorescence staining and immunoprecipitation. ResultsThe expression of -arrestin-1 was significantly increased and colocalized with CD45-positive cells in spinal cord of experimental auto-immune encephalomyelitis (EAE) mice when compared with the sham mice, which was attenuated by pretreatment with PNU282987, a specific 7nAChR agonist. PNU282987 also significantly inhibited the activation of NLRP3 inflammasome and thus decreased the production of IL-1 and IL-18 both in lipopolysaccharide (LPS)/ATP-stimulated BV2 microglia in vitro and spinal cord from EAE mice in vivo, while inverse effects were observed in 7nAChR knockout mice. Furthermore, overexpression of -arrestin-1 attenuated the inhibitory effect of PNU282987 on NLRP3 inflammasome activation in LPS/ATP-stimulated BV2 microglia. PNU282987 inhibited the interaction between -arrestin-1 and NLRP3 protein in vitro. ConclusionsThe present study demonstrates that activating 7nAChR can lead to NLRP3 inflammasome inhibition via regulation of -arrestin-1 in monocyte/microglia system.
- 出版日期2017-11
- 单位浙江省农业科学院; 中国人民解放军第二军医大学
