Curcumin suppresses NLRP3 inflammasome activation and protects against LPS-induced septic shock
作者单位：Xinhua Hospital Shanghai Jiaotong University School of Medicine Shanghai Institute for Pediatric Research
会议名称：《第十届全国免疫学学术大会》
会议日期：2015年
学科分类：1008[医学-中药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学]
关 键 词：inflammasome curcumin anti-inflammation
摘 要：Objective: The NLRP3 inflammasome responds to various pathogen-derived factors and danger-associated molecules, mediating IL-1β maturation, therefore is involved in multiple inflammatory diseases, including septic shock. Strategies aimed at modulation of its activation may represent an appealing treatment for inflammatory diseases it contributes to. Curcumin has been shown to possess strong anti-inflammatory activity, but the underlying mechanism is not fully understood. In this study, we sought to investigate the role and mechanism of curcumin on the inhibition of mature IL-1β production via the regulation of NLRP3 inflammasome as well as its effect on the prevention of LPS- induced septic ***: The secretion of IL-1β and HMGB-1 was detected by western blot and ELISA. Intracellular K+ level was determined by ICP-OES assay. Lysosomal disruption and ROS formation were measured by fluorescent ***: Curcumin dramatically inhibited the production of mature IL-1β in LPS-primed macrophages triggered by mul-tiple NLRP3 inflammasome activators, and also reduced the level of cleaved caspase-1. Curcumin prevented K+ efflux and attenuated lysosomes disruption and intracellular ROS formation as well. The inhibition of NLRP3 inflammasome by curcumin was in part mediated via the suppression of extracellular regulated protein kinases phosphorylation. Furthermore, administration of curcumin significantly reduced peritoneal IL-1β and HMGB-1 concentration induced by LPS and improved the survival of mice suffering from lethal endotoxic ***: Curcumin potently inhibits the activation of NLRP3 inflammasome which may contribute to its anti-inflammatory activity. Our finding offers a mechanistic basis for the therapeutic potential of curcumin in septic shock and other NLRP3 inflammasome-driven diseases.