Basic-alimentary tractStress-induced disruption of colonic epithelial barrier: role of interferon-γ and myosin light chain kinase in mice☆
Section snippets
Animals
All experiments were approved by the local institutional Animal Care and Use Committee. Seven-week-old female Swiss 3T3 mice (Harlan, Gannat, France) and B6-SCID mice (Iffa-Credo, Saint Germain sur l’Arbresle, France) were used. Female B6-Ifng−/− mice20 were obtained from Jackson Laboratory (Bar Harbor, ME), bred, and maintained in the animal facility of the Institut Fédératif de Recherche Claude De Preval (INSERM IFR 30, Toulouse, France). Female C57BL/6J (Elevage Janvier, Le Genest St-Isle,
Colon, liver, and spleen histologic alterations
No histologic alteration of colon and splenic tissues of control and stressed mice was observed. Similarly, no myeloperoxidase activity increase was noted, showing the absence of granulocyte infiltrate (data not shown). In contrast, microscopic hepatic lesions were found in stressed mice compared with controls (Figure 1). Lesions observed in stressed mice were characterized by apoptotic hepatocytes with picnotic nuclei reaching about 15% of all hepatocytes and a thickening of bile ducts
Discussion
This study brings novel data regarding the mechanisms through which stress disrupts the colonic barrier function, and the pathophysiologic consequences of this alteration. We first observed that, in the colon, an enhanced expression of IFN-γ occurred early (day 1), whereas increased colonic paracellular permeability was observed later (day 4). These alterations were not associated with modifications of the architectural structure of the colonic mucosa of stressed Swiss mice. We also showed that
Acknowledgements
The authors thank Valerie Geronimo and Caroline Bisiaux for their skillful technical assistance, and Dr. Neil Ledger for critical reading of the manuscript.
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Supported by Institut de Recherche sur les Maladies de l’Affareil Digestif (IRMAD), Fondation pour la Recherche Médicale, and an institutional grant of Institut National de la Recherche Agronomique. L.M. is a recipient of the Ministère de l’Education Nationale, de l’Enseignement Supérieur, de la Recherche, et de la Technologie.