title: Curcumin suppresses NLRP3 inflammasome activation and protects against LPS-induced septic shock.
abstract: METHODS
  The NLRP3 inflammasome responds to various pathogen-derived factors and danger-associated molecules, mediating IL-1β maturation, therefore is involved in multiple inflammatory diseases. Curcumin has been shown to possess strong anti-inflammatory activity, but the underlying mechanism is not fully understood. Here, we sought to investigate the role and mechanism of curcumin on the inhibition of mature IL-1β production via the regulation of NLRP3 inflammasome.
  
  
  RESULTS
  Curcumin dramatically inhibited the production of mature IL-1β in LPS-primed macrophages triggered by multiple NLRP3 inflammasome activators, and also reduced the level of cleaved caspase-1 as measured by western blot and ELISA. Curcumin prevented K(+) efflux, the common trigger for NLRP3 inflammasome activation, 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 shock.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of pediatric Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P. R. China.|Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, P. R. China.|Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, P. R. China.
authors.forename: Zizhen
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Department of pediatric Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P. R. China.|Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, P. R. China.|Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, P. R. China.
authors.forename: Jiefei
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Shanghai institute of Health Science, Shanghai, P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Geriatrics, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P. R. China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai Jiaotong University School of Medicine, Shanghai, P. R. China.
authors.forename: Congfeng
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of pediatric Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P. R. China.|Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, P. R. China.|Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, P. R. China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, P. R. China.|Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, P. R. China.
authors.forename: Yingwei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of pediatric Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P. R. China.|Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, P. R. China.|Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of pediatric Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P. R. China.|Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, P. R. China.|Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, P. R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D020170:Caspase 1 / Q000378:metabolism; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000378:metabolism; D058847:Inflammasomes / Q000187:drug effects* / Q000502:physiology; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008247:Lysosomes / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012772:Shock, Septic / Q000517:prevention & control*
chemical_list: D000893:Anti-Inflammatory Agents; D024243:HMGB1 Protein; D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D017382:Reactive Oxygen Species; D020170:Caspase 1; D003474:Curcumin; D011188:Potassium
keywords: Anti-inflammation; Curcumin; IL-1β; Inflammasome; MAPK