Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Polychlorinated biphenyls disrupt intestinal integrity via NADPH oxidase-induced alterations of tight junction protein expression.

Authors: Choi, Yean Jung; Seelbach, Melissa J; Pu, Hong; Eum, Sung Yong; Chen, Lei; Zhang, Bei; Hennig, Bernhard; Toborek, Michal

Published In Environ Health Perspect, (2010 Jul)

Abstract: Polychlorinated biphenyls (PCBs) are widely distributed environmental toxicants that contribute to numerous disease states. The main route of exposure to PCBs is through the gastrointestinal tract; however, little is known about the effects of PCBs on intestinal epithelial barrier functions.The aim of the present study was to address the hypothesis that highly chlorinated PCBs can disrupt gut integrity at the level of tight junction (TJ) proteins.Caco-2 human colon adenocarcinoma cells were exposed to one of the following PCB congeners: PCB153, PCB118, PCB104, and PCB126. We then assessed NAD(P)H oxidase (NOX) activity and expression and the barrier function of Caco-2 cells. In addition, the integrity of intestinal barrier function and expression of TJ proteins were evaluated in C57BL/6 mice exposed to individual PCBs by oral gavage.Exposure of Caco-2 cells to individual PCB congeners resulted in activation of NOX and increased permeability of fluorescein isothiocyanate (FITC)-labeled dextran (4 kDa). Treatment with PCB congeners also disrupted expression of TJ proteins zonula occludens-1 (ZO-1) and occludin in Caco-2 cells. Importantly, inhibition of NOX by apocynin significantly protected against PCB-mediated increase in epithelial permeability and alterations of ZO-1 protein expression. Exposure to PCBs also resulted in alterations of gut permeability via decreased expression of TJ proteins in an intact physiological animal model.These results suggest that oral exposure to highly chlorinated PCBs disrupts intestinal epithelial integrity and may directly contribute to the systemic effects of these toxicants.

PubMed ID: 20299304 Exiting the NIEHS site

MeSH Terms: Analysis of Variance; Animals; Blotting, Western; Caco-2 Cells; Electrophoresis, Polyacrylamide Gel; Environmental Pollutants/toxicity*; Enzyme Activation/drug effects; Fluorescent Antibody Technique; Humans; Immunohistochemistry; Immunoprecipitation; Intestinal Mucosa/drug effects*; Male; Membrane Proteins/metabolism; Mice; Mice, Inbred C57BL; NADPH Oxidases/metabolism*; Occludin; Phosphoproteins/metabolism; Polychlorinated Biphenyls/toxicity*; Tight Junctions/drug effects*; Zonula Occludens-1 Protein

Back
to Top