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

Yean Jung Choi, Melissa J. Seelbach, H. Pu, Sung Yong Eum, Lei Chen, Bei Zhang, Bernhard Hennig, Michal Toborek

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Original languageEnglish
Pages (from-to)976-981
Number of pages6
JournalEnvironmental Health Perspectives
Volume118
Issue number7
DOIs
Publication statusPublished - 2010

Fingerprint

Tight Junction Proteins
NADPH Oxidase
Polychlorinated Biphenyls
Caco-2 Cells
Permeability
Zonula Occludens-1 Protein
Occludin
Tight Junctions
Inbred C57BL Mouse
Gastrointestinal Tract
Colon
Adenocarcinoma
Animal Models

Keywords

  • Caco-2 cells
  • Intestine
  • Oxidative stress
  • Polychlorinated biphenyls
  • Tight junctions

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Public Health, Environmental and Occupational Health
  • Medicine(all)

Cite this

Polychlorinated biphenyls disrupt intestinal integrity via NADPH oxidase-induced alterations of tight junction protein expression. / Choi, Yean Jung; Seelbach, Melissa J.; Pu, H.; Eum, Sung Yong; Chen, Lei; Zhang, Bei; Hennig, Bernhard; Toborek, Michal.

In: Environmental Health Perspectives, Vol. 118, No. 7, 2010, p. 976-981.

Research output: Contribution to journalArticle

Choi, Yean Jung ; Seelbach, Melissa J. ; Pu, H. ; Eum, Sung Yong ; Chen, Lei ; Zhang, Bei ; Hennig, Bernhard ; Toborek, Michal. / Polychlorinated biphenyls disrupt intestinal integrity via NADPH oxidase-induced alterations of tight junction protein expression. In: Environmental Health Perspectives. 2010 ; Vol. 118, No. 7. pp. 976-981.
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AU - Seelbach, Melissa J.

AU - Pu, H.

AU - Eum, Sung Yong

AU - Chen, Lei

AU - Zhang, Bei

AU - Hennig, Bernhard

AU - Toborek, Michal

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N2 - BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

AB - BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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