Effects of alcohol on intestinal epithelial barrier permeability and expression of tight junction-associated proteins

Mol Med Rep. 2014 Jun;9(6):2352-6. doi: 10.3892/mmr.2014.2126. Epub 2014 Apr 9.

Abstract

The present study aimed to investigate the effects of alcohol on intestinal epithelial barrier permeability and expression of the tight junction-associated proteins, zonula occludens-1 (ZO-1) and claudin-1. An alcohol-treated Caco-2 intestinal epithelial cell monolayer in vitro model was used to investigate whether alcohol is able to induce intestinal barrier dysfunction and decrease expression of ZO-1 and claudin-1. MTT assay results revealed unaltered cell viability at alcohol concentrations of <5%. Caco-2 cells in the 5% alcohol-treated groups exhibited a significant time-dependent decrease in transepithelial electrical resistance (TEER) and an increase in fluorescent yellow flux rate compared with the control cells. ZO‑l expression exhibited a progressive decline following 20 min of incubation, reached its minimum levels at 60 min and then showed an increasing trend following 60 min of incubation. In addition, claudin-1 expression exhibited a progressive increase following 60 min of incubation, reached its maximum levels at 60 min and then showed an increasing trend following 60 min of incubation. Alterations in the expression of the ZO-l and claudin-1 proteins revealed trends consistent with changes in the TEER value and the fluorescent yellow transmittance rate in the Caco-2 cells. The results of this study indicate that alcohol is able to increase the intestinal epithelial barrier permeability in a dose- and time-dependent manner. Alcohol induces a change in the expression of the tight junction-associated proteins, ZO-1 and claudin-1, which are two major sites of alcohol action, thus increasing intestinal epithelial barrier permeability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Cell Survival / drug effects
  • Claudin-1 / genetics
  • Claudin-1 / metabolism
  • Ethanol / metabolism*
  • Ethanol / pharmacology
  • Gene Expression Regulation
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism*
  • Permeability / drug effects
  • Protein Transport
  • Tight Junction Proteins / genetics
  • Tight Junction Proteins / metabolism*
  • Zonula Occludens-1 Protein / genetics
  • Zonula Occludens-1 Protein / metabolism

Substances

  • Claudin-1
  • Tight Junction Proteins
  • Zonula Occludens-1 Protein
  • Ethanol