Lidocaine Suppresses NLRP3 Inflmmasome Expression By CAMP/PKA Signaling Pathway

Objectives Observing the effects of lidocaine on expression of NLRP3 inflammasome in lipopolysaccharide-induced acute inflammation responses, to investigate whether lidocaine negatively regulates the expression of NLRP3 inflammasome in lipopolysaccharide-induce THP-1 macrophagocyte by c AMP/PKA signaling pathway.Methods THP-1 monocytes as the research object, treated with PMA to become THP-1 macrophages, form a inflammation model by LPS. Cells are divided into five groups: Normal Control groups are normal THP-1 macrophagocyte; Lidocaine groups are THP-1 m acrophagocyte treated by 20ug/ml lidocaine for 24h; LPS groups are THP-1 macrophages stimulated by 10ng/ml LPS for 6h; LPS+lidoc aine groups are THP-1 macrophages pretreated by 20ug/ml lidocaine for 24 h and then stimulated by 10ng/ml LPS for 6h; blockers groups(LPS+lidocaine+M) are THP-1 macrophages pre-treated by lidoc-aine 20ug/ml for 24 h, then stimulated with 10ng/ml LPS for 6h, fi-nally 10?mol/l MDL-12,330A(M) is added for 30min; ELISA is analysis for IL-1?, IL-18 content in cell culture supernatant; NLRP3 inflammasome protein-associated NLRP3, Caspase-1 and ASC protein expression are measured by Western blotting, and semi-quantitative analysis.Results 1. The results of ELISA showed cytokines of IL-1?, IL-18 in LPS+lidocaine groups decreased obviously by Comparing with LPS groups. Western Blot results showed NLRP3, ASC and Caspase-1 protein expression decreased; compared with the Control group, Lidocaine groups inflammatory cytokines and protein expression have no significant changes. It describes that lidocaine can negatively regulate the expression of macrophage NLRP3 inflammasome on THP-1 macrophages induced by LPS, however, in the non-inflammatory state, lidocaine had no obvious effects on THP-1 macrophages. 2. Compared with LPS + lidocaine group, LPS + lidocaine + M groups cytokines IL-1?, IL-18 expression significantly increased, and the expression of NLRP3, ASC and Caspase-1 protein also significantly increased; compared with LPS group, There is no significant difference in LPS + lidocaine + M group inflammation. the negative regulatory of NLRP3 inflammasome by lidocaine disappeared, which indicated that deactivation of c AMP/PKA signaling pathway abrogated the effection of lidocaine on LPS-induced NLRP3 inflammasome expression.Conclusion Lidocaine reduces LPS-induced IL-1?, IL-18 release in THP-1 macrophages, suppresses NLRP3 inflammasome expression by c AMP/PKA signaling pathway.