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Intestinal epithelial barrier function is disrupted by acrolein, an environmental/dietary pollutant and lipid metabolite
Author(s) -
Chen WeiYang,
Zhang Jingwen,
Barve Shirish,
McClain Craig,
JoshiBarve Swati
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1067.9
Subject(s) - barrier function , acrolein , lipopolysaccharide , tight junction , intestinal permeability , occludin , intestinal epithelium , paracellular transport , intestinal mucosa , chemistry , biology , microbiology and biotechnology , biochemistry , immunology , permeability (electromagnetism) , epithelium , medicine , genetics , membrane , catalysis
The gastrointestinal epithelial barrier function is critical for maintaining selective gut permeability that limits the entry of bacteria and pathological bacterial components (e.g., endotoxin, lipopolysaccharide‐LPS) into systemic circulation, which can result in inflammation and injury. Clinical and experimental studies suggest that intestinal barrier dysfunction (“leaky gut”) can predispose to or enhance chronic inflammatory intestinal and non‐intestinal disorders, such as diabetes, IBD, alcoholic liver disease and autoimmune diseases, etc. Many environmental and dietary factors are thought to alter intestinal epithelium leading to gut permeability and bacterial translocation. Acrolein is an environmental and dietary pollutant, and a lipid‐derived metabolite. This study evaluates the effects of acrolein on intestinal epithelial barrier function and permeability, both in vitro and in vivo. Our data demonstrate that oral acrolein exposure in mice caused intestinal barrier permeability leading to increased translocation of bacterial endotoxin/lipopolysaccharide into the blood. Also, acrolein adversely affected the barrier integrity of a polarized Caco‐2 monolayer, as demonstrated by a decrease in transepithelial electrical resistance (TEER), with a corresponding increase in barrier permeability to a fluorescent dye (FD‐4). Acrolein exposure resulted in the downregulation and delocalization/redistribution of key tight junction proteins (TJP, e.g., zonula occludens‐1, claudin‐1 and occludin) that critically regulate epithelial paracellular permeability. In addition to TJP alterations, acrolein also caused epithelial cell death by apoptosis, which is known to be a significant mechanism that contributes to intestinal barrier dysfunction and permeability in inflammatory bowel diseases. Overall, we demonstrate that exposure to acrolein has a major impact on the intestinal epithelium that involves (i) decrease/redistribution and discontinuous localization of TJPs, and (ii) epithelial cell apoptosis, thereby resulting in loss of barrier integrity/function and permeability. Our findings highlight the adverse consequences of environmental and dietary pollutants/factors on intestinal barrier dysfunction that may contribute to gut permeability and bacterial translocation. Support or Funding Information Supported by NIH and Veterans Administration.