Decreased epithelial barrier function evoked by exposure to metabolic stress and nonpathogenic E. coli is enhanced by TNF-alpha

American Journal of Physiology. Gastrointestinal and Liver Physiology
Kimberley LewisDerek M McKay

Abstract

A defect in mitochondrial activity contributes to many diseases. We have shown that monolayers of the human colonic T84 epithelial cell line exposed to dinitrophenol (DNP, uncouples oxidative phosphorylation) and nonpathogenic Escherichia coli (E. coli) (strain HB101) display decreased barrier function. Here the impact of DNP on macrophage activity and the effect of TNF-alpha, DNP, and E. coli on epithelial permeability were assessed. DNP treatment of the human THP-1 macrophage cell line resulted in reduced ATP synthesis, and, although hyporesponsive to LPS, the metabolically stressed macrophages produced IL-1beta, IL-6, and TNF-alpha. Given the role of TNF-alpha in inflammatory bowel disease (IBD) and the association between increased permeability and IBD, recombinant TNF-alpha (10 ng/ml) was added to the DNP (0.1 mM) + E. coli (10(6) colony-forming units), and this resulted in a significantly greater loss of T84 epithelial barrier function than that elicited by DNP + E. coli. This increased epithelial permeability was not due to epithelial death, and the enhanced E. coli translocation was reduced by pharmacological inhibitors of NF-kappabeta signaling (pyrrolidine dithiocarbamate, NF-kappabeta essential modifier-binding pepti...Continue Reading

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Citations

Jun 16, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Ida SchoultzDerek M McKay
Oct 18, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·Maciej Chichlowski, Laura P Hale
Jul 19, 2012·World Journal of Gastroenterology : WJG·Alan B R ThomsonHugh Freeman
Jul 19, 2014·The American Journal of Pathology·Arthur WangDerek M McKay
Nov 2, 2015·Redox Biology·Fabiana Andréa MouraMarília Oliveira Fonseca Goulart
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Aug 11, 2011·Inflammatory Bowel Diseases·Ida SchoultzDerek M McKay
Dec 22, 2009·Inflammatory Bowel Diseases·Kimberley LewisDerek M McKay
Jun 10, 2017·World Journal of Gastroenterology : WJG·Nandakumar PackiriswamyLorraine M Sordillo
Mar 10, 2020·Annals of Coloproctology·Martin ŠašalaIveta Fandáková
Mar 3, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Derek M McKayTimothy Shutt
Jan 24, 2018·World Journal of Gastroenterology : WJG·Na Li, Rui-Hua Shi
Jun 23, 2009·Annals of the New York Academy of Sciences·Kimberley Lewis, Derek M McKay
Oct 27, 2020·JGH Open : an Open Access Journal of Gastroenterology and Hepatology·Hagamenon de Alencar JuniorOrlando Ambrogini-Júnior

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