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Decreased epithelia...
Decreased epithelial barrier function evoked by exposure to metabolic stress and nonpathogenic E. coli is enhanced by TNF-a
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- Lewis, K. (författare)
- Intestinal Disease Research Programme, McMaster University, Hamilton, ON, Canada
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- Caldwell, J. (författare)
- Gastrointestinal Research Group, Department of Physiology and Biophysics, University of Calgary, Calgary, AB, Canada
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- Phan, V. (författare)
- Gastrointestinal Research Group, Department of Physiology and Biophysics, University of Calgary, Calgary, AB, Canada
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- Prescott, D. (författare)
- Gastrointestinal Research Group, Department of Physiology and Biophysics, University of Calgary, Calgary, AB, Canada
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- Nazli, A. (författare)
- Intestinal Disease Research Programme, McMaster University, Hamilton, ON, Canada
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- Wang, A. (författare)
- Gastrointestinal Research Group, Department of Physiology and Biophysics, University of Calgary, Calgary, AB, Canada
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- Söderholm, Johan D (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Hälsouniversitetet,Kirurgi,Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala
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- Perdue, M.H. (författare)
- Intestinal Disease Research Programme, McMaster University, Hamilton, ON, Canada
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- Sherman, P.M. (författare)
- Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
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- McKay, D.M. (författare)
- Gastrointestinal Research Group, Department of Physiology and Biophysics, University of Calgary, Calgary, AB, Canada, Gastrointestinal Research Group, Dept. Physiology and Biophysics, Univ. of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada
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(creator_code:org_t)
- American Physiological Society, 2008
- 2008
- Engelska.
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Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 294:3
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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-a, 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-1ß, IL-6, and TNF-a. Given the role of TNF-a in inflammatory bowel disease (IBD) and the association between increased permeability and IBD, recombinant TNF-a (10 ng/ml) was added to the DNP (0.1 mM) + E. coli (106 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-?ß signaling (pyrrolidine dithiocarbamate, NF-?ß essential modifier-binding peptide, BAY 11-7082, and the proteosome inhibitor, MG132). In contrast, the drop in transepithelial electrical resistance was unaffected by the inhibitors of NF-?ß. Thus, as an integrative model system, our findings support the induction of a positive feedback loop that can severely impair epithelial barrier function and, as such, could contribute to existing inflammation or trigger relapses in IBD. Thus metabolically stressed epithelia display increased permeability in the presence of viable nonpathogenic E. coli that is exaggerated by TNF-a released by activated immune cells, such as macrophages, that retain this ability even if they themselves are experiencing a degree of metabolic stress. Copyright © 2008 the American Physiological Society.
Nyckelord
- Bacterial translocation
- Macrophages
- NF?B
- Permeability
- T84 cells
- MEDICINE
- MEDICIN
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- art (ämneskategori)
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- Av författaren/redakt...
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Lewis, K.
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Caldwell, J.
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Phan, V.
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Prescott, D.
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Nazli, A.
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Wang, A.
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visa fler...
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Söderholm, Johan ...
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Perdue, M.H.
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Sherman, P.M.
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McKay, D.M.
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- Artiklar i publikationen
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American Journal ...
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Linköpings universitet