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Author Notes:

Correspondence: Daniel M. Chopyk, Division of Digestive Diseases, 615 Michael Street NE, Suite 265, Atlanta, GA 30322. Tel: +1 404 727 2862; Fax: +1 404 727 5767; Email: dchopyk@emory.edu

The authors thank Dr. Jason Matthews (Emory University, Atlanta, GA) for providing Caco‐2 cells and Dr. Peijian He (Emory University, Atlanta, GA) for providing SK‐CO15 and HEK293T cells, as well as for providing for providing pLTR‐G and PCD/NL‐BH4 plasmids and technical aid in preparing lentiviral vectors.

The authors additionally thank Dr. Chris Yun (Emory University, Atlanta, GA) for usage of EMD Millipore Millicell‐ERS Volt‐Ohm meter.

The authors have no conflicts of interest.


Research Funding:

This research project was supported in part by the Emory University Integrated Cellular Imaging Microscopy Core of the Emory and Children's Pediatric Research Center.

We also acknowledge the Animal and Morphology Core facilities of the NIAAA‐supported Southern California Research Center for ALPD and Cirrhosis (P50 AA011999) for providing support in designing mouse diets and in carrying out all animal ethanol feeding studies.

This work was supported by NIH grant F31AA024960 to DMC; NIH grants DK062092, DK113147, and DK111678 to FAA; and NIH grant DK110264 to RR.

A portion of this work was also supported by funds provided by Emory University.


  • Caco‐2
  • Junctional adhesion molecule‐A
  • Rap2
  • ethanol
  • intestinal epithelial barrier
  • myosin light chain kinase

Dysregulation of junctional adhesion molecule-a contributes to ethanol-induced barrier disruption in intestinal epithelial cell monolayers


Journal Title:

Physiological Reports


Volume 5, Number 23


, Pages e13541-e13541

Type of Work:

Article | Final Publisher PDF


Alcohol consumption promotes loss of intestinal barrier function. However, mechanisms by which ethanol affects the tight junction (TJ), the cellular structure responsible for maintaining the gut epithelial barrier, are not well understood. Three classes of transmembrane proteins comprise TJs: occludin, claudins, and junctional adhesion molecules (JAMs). It has recently been postulated that JAM-A (F11R), the most abundant JAM expressed in intestinal epithelium, regulates “leak” pathway flux, a paracellular route for the nonse-lective permeation of large solutes. Since transluminal flux of many gut-derived antigens occurs through this pathway, we investigated the role of JAM-A in ethanol-induced disruption of the intestinal epithelial barrier. Using Caco-2 and SK-CO15 monolayers, we found that ethanol induced a dose- and time-dependent decrease in JAM-A protein expression to about 70% of baseline levels. Alcohol also reduced Ras-related protein 2 (Rap2) activity, and enhanced myosin light chain kinase (MLCK) activity, changes consistent with impaired JAM-A signaling. Stable overexpression and shRNA-mediated knockdown of JAM-A were employed to investigate the role of JAM-A in paracellu-lar-mediated flux following alcohol exposure. The paracellular flux of 40-kDa fluorescein isothiocynate (FITC)-dextran following ethanol treatment was decreased by the overexpression of JAM-A; conversely, flux was enhanced by JAM-A knockdown. Thus, we conclude that ethanol-mediated control of JAM-A expression and function contributes to mechanisms by which this chemical induces intestinal epithelial leakiness.

Copyright information:

© 2017 The Authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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