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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Autophagy down-regulates NLRP3-dependent inflammatory response of intestinal epithelial cells under nutrient deprivation

  • Yun, Yewon (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Baek, Ahruem (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Kim, Dong-Eun (Department of Bioscience and Biotechnology, Konkuk University)
  • Received : 2020.09.25
  • Accepted : 2020.12.11
  • Published : 2021.05.31
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Abstract

Dysregulation of inflammation induced by noninfectious stress conditions, such as nutrient deprivation, causes tissue damage and intestinal permeability, resulting in the development of inflammatory bowel diseases. We studied the effect of autophagy on cytokine secretion related to intestinal permeability under nutrient deprivation. Autophagy removes NLRP3 inflammasomes via ubiquitin-mediated degradation under starvation. When autophagy was inhibited, starvation-induced NLRP3 inflammasomes and their product, IL-1β, were significantly enhanced. A prolonged nutrient deprivation resulted in an increased epithelial mesenchymal transition (EMT), leading to intestinal permeability. Under nutrient deprivation, IL-17E/25, which is secreted by IL-1β, demolished the intestinal epithelial barrier. Our results suggest that an upregulation of autophagy maintains the intestinal barrier by suppressing the activation of NLRP3 inflammasomes and the release of their products, including pro-inflammatory cytokines IL-1β and IL-17E/25, under nutrient deprivation.

Keywords

Acknowledgement

This research was supported by grants from the National Research Foundation of Korea (2017R1E1A1A01074656) funded by the Korean government. We would like to thank Editage (www.editage.co.kr) for English language editing.

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