title: Deoxycholic Acid Triggers NLRP3 Inflammasome Activation and Aggravates DSS-Induced Colitis in Mice.
abstract: A westernized high-fat diet (HFD) is associated with the development of inflammatory bowel disease (IBD). High-level fecal deoxycholic acid (DCA) caused by HFD contributes to the colonic inflammatory injury of IBD; however, the mechanism concerning the initiation of inflammatory response by DCA remains unclear. In this study, we sought to investigate the role and mechanism of DCA in the induction of inflammationviapromoting NLRP3 inflammasome activation. Here, we, for the first time, showed that DCA dose-dependently induced NLRP3 inflammasome activation and highly pro-inflammatory cytokine-IL-1β production in macrophages. Mechanistically, DCA-triggered NLRP3 inflammasome activation by promoting cathepsin B release at least partially through sphingosine-1-phosphate receptor 2. Colorectal instillation of DCA significantly increased mature IL-1β level in colonic tissue and exacerbated DSS-induced colitis, whilein vivoblockage of NLRP3 inflammasome or macrophage depletion dramatically reduced the mature IL-1β production and ameliorated the aggravated inflammatory injury imposed by DCA. Thus, our findings show that high-level fecal DCA may serve as an endogenous danger signal to activate NLRP3 inflammasome and contribute to HFD-related colonic inflammation. NLRP3 inflammasome may represent a new potential therapeutical target for treatment of IBD.
authors.affiliation: Department of Pediatric Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Pediatric Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, 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, China; Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
authors.forename: Jiefei
authors.initials: J
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Proteomics, National Center for Proteomics Science, Beijing Institute of Radiation Medicine, Beijing, China; National Engineering Research Center for Protein Drugs, Beijing, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Tian
authors.affiliation: Department of Geriatrics, Xinhua Hospital, Shanghai Jiaotong University School of Medicine , Shanghai , 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 , China.
authors.forename: Congfeng
authors.initials: C
authors.lastname: Xu
authors.affiliation: Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, 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, China; Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, 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, China; Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wu
keywords: IL-1β; bile acid; high-fat diet; inflammasome; inflammation; inflammatory bowel disease