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

• 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
• ISSN: 0363-6143; 1522-1563

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]