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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

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

¹Section of Gastrointestinal Sciences, Faculty of Medicine, University of Manchester, Salford M6 5HD; and ²School of Informatics, University of Wales, Bangor LL57 1UT, United Kingdom

Submitted 7 January 2004 ; accepted in final form 28 June 2004

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.

Caco-2; intestinal permeability

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