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Am J Physiol Cell Physiol 287: C1412-C1417, 2004. First published June 30, 2004; doi:10.1152/ajpcell.00007.2004
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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

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

John McLaughlin,1 Philip J. Padfield,1 Julian P. H. Burt,2 and Catherine A. O'Neill1

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



Address for reprint requests and other correspondence: C. A. O'Neill, Section of Gastrointestinal Sciences, Univ. of Manchester Faculty of Medicine, Clinical Sciences Bldg., Hope Hospital, Salford M6 5HD, United Kingdom (E-mail: coneill{at}fs1.ho.man.ac.uk)




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