Alcohol accumulation promotes esophagitis via pyroptosis activation

Int J Biol Sci. 2018 Jul 13;14(10):1245-1255. doi: 10.7150/ijbs.24347. eCollection 2018.

Abstract

Gastroesophageal reflux impairs the mucosal barrier in the distal esophagus, allowing chronic exposure of the squamous epithelium to multitudinous stimulations and inducing chronic inflammation. Esophagitis is a response to inflammation of the esophageal squamous mucosa. Our study clarified that alcohol accumulation could aggravate the progress of esophagitis by inducing pyroptosis; however, Ac-YVAD-CMK, an inhibitor of caspase-1, could effectively suppress the expression of IL-1β and IL-18 both in vivo and in vitro, reducing the inflammatory response, which is promised to be an agent to inhibit the progression of esophagitis. Additionally, caspase-1-derived pyroptosis is involved in esophageal cancer.

Keywords: Ac-YVAD-CMK; alcohol; caspase-1; esophagitis; pyroptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Caspase 1 / metabolism*
  • Cell Line
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Enzyme Activation / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Esophagitis / chemically induced*
  • Esophagitis / metabolism*
  • Ethanol / pharmacology*
  • Humans
  • Immunohistochemistry
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pyroptosis / drug effects*

Substances

  • Interleukin-18
  • Interleukin-1beta
  • Ethanol
  • Caspase 1