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 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 approximately 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 immunofluorescence 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.
McLaughlin
John
J
Section of Gastrointestinal Sciences, Faculty of Medicine, University of Manchester, Salford M6 5HD, United Kingdom.
Padfield
Philip J
PJ
Burt
Julian P H
JP
O'Neill
Catherine A
CA
D018938:Caco-2 Cells; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D017097:Electric Impedance; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D008565:Membrane Proteins / Q000187:drug effects* / Q000378:metabolism; D018613:Microscopy, Confocal; D009793:Ochratoxins / Q000494:pharmacology*; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism
D002121:Calcium Channel Blockers; D008565:Membrane Proteins; D009793:Ochratoxins; C025589:ochratoxin A