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Original Research ARTICLE

Front. Immunol. | doi: 10.3389/fimmu.2016.00536

Deoxycholic acid triggers NLRP3 inflammasome activation and aggravates DSS-induced colitis in mice

Jin Wu1*, Shengnan Zhao1, Zizhen Gong1, Jiefei Zhou1, Chunyan Tian3, Yanhong Gao1, Congfeng Xu2, Yingwei Chen1 and Wei Cai1
  • 1Xinhua hospital, Shanghai Jiaotong University School of Medicine, China
  • 2Institutes of Medical Sciences, Shanghai Jiaotong University School of Medicine, China
  • 3Beijing Institute of Radiation Medicine, China

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 inflammation via promoting 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 (S1PR2). Colorectal instillation of DCA significantly increased mature IL-1β level in colonic tissue and exacerbated DSS-induced colitis, while in vivo blockage 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 contributes to HFD-related colonic inflammation. NLRP3 inflammasome may represent a new potential therapeutical target for treatment of IBD.

Keywords: high fat diet, Bile acid, Inflammation, Inflammasome, IL-1beta, Inflammatory Bowel Diseases

Citation: Wu J, Zhao S, Gong Z, Zhou J, Tian C, Gao Y, Xu C, Chen Y and Cai W (2016). Deoxycholic acid triggers NLRP3 inflammasome activation and aggravates DSS-induced colitis in mice. Front. Immunol. 7:536. doi: 10.3389/fimmu.2016.00536

Received: 20 Sep 2016; Accepted: 14 Nov 2016.

Edited by:

Lorraine M. Sordillo, Michigan State University, USA

Reviewed by:

Nobuhiko Kamada, University of Michigan Health System, USA
Alberto Finamore, Council for Agricultural Research and Economics-Food and Nutrition Research Center, Italy, Italy  

Copyright: © 2016 Wu, Zhao, Gong, Zhou, Tian, Gao, Xu, Chen and Cai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Jin Wu, Xinhua hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China, wujin51@yahoo.com