Ochratoxin A increases permeability through tight junctions by removal of specific claudin isoforms

On interaction with the intestine, the mycotoxin ochratoxin A is know to cause rapid inflammation, diarrhea, and increased bacterial translocation. All these effects are consistent with a decrease in epithelial barrier function. However, this has not been shown directly. We determined that ochratoxi...

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Bibliographic Details
Published in:American Journal of Physiology: Cell Physiology 2004-11, Vol.56 (5), p.C1412-C1417
Main Authors: MCLAUGHLIN, John, PADFIELD, Philip J, BURT, Julian P. H, O'NEILL, Catherine A
Format: Article
Language:English
Subjects:
Bacteria
Biological and medical sciences
Cell interactions, adhesion
Cell physiology
Cellular biology
Diarrhea
Digestive system
Fundamental and applied biological sciences. Psychology
Membrane and intracellular transports
Molecular and cellular biology
Toxins
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Summary:On interaction with the intestine, the mycotoxin ochratoxin A is know to cause rapid inflammation, diarrhea, and increased bacterial translocation. All these effects are consistent with a decrease in epithelial barrier function. However, this has not been shown directly. We determined that ochratoxin A is able to reduce the barrier properties of the model intestinal cell line Caco-2. Over 24 h, ochratoxin A reduces the transepithelial electrical resistance of Caco-2 monolayers growing on Transwell filters by 40%. At the same time, the permeability of the monolayer is increased with respect to 4- and 10-kDa FITC dextrans, but not to 20- or 40-kDa dextrans. Immunoblotting and immuofluorescence reveal that the decrease in barrier properties is concomitant with disappearance of claudins 3 and 4, but not claudin 1 from Caco-2 cell membranes. These results suggest that ochratoxin A is able to modulate the barrier function of Caco-2 cells by removal of specific claudin isoforms. [PUBLICATION ABSTRACT]
ISSN:0363-6143
1522-1563