Cellular Localization, Binding Sites, and Pharmacologic Effects of TFF3 in Experimental Colitis in Mice
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Trefoil factors (TFFs) are essential for protection and restitution of the gastrointestinal mucosa but many aspects of TFF biology are unclear. Our aim was to compare the localization of endogenous TFFs and binding sites for injected TFF3 in the colon of healthy and colitic mice and to study the effect of TFF3 on dextrane sulfate sodium (DSS)-induced colitis in mice. Expression of endogenous TFF1-3 was examined by in situ hybridization and immunohistochemistry, and the distribution of intravenously, intraperitoneally, and subcutaneously administered 125I-TFF3 by autoradiography and gamma-counting. The effect of systemically administered TFF3 on DSS-induced colitis was assessed. We found increased expression of endogenous TFF3 and increased binding of injected 125I-TFF3 in the colon of animals with DSS-induced colitis. The distribution of intraperitoneally and subcutaneously administered 125I-TFF3 was comparable. Systemic administration of the peptides reduced the severity of colitis. Expression of endogenous TFF3 and binding of systemically administered TFF3 are increased in DSS-induced colitis. Systemic administration of TFF3 attenuates the disease. These findings suggest a role of TFF3 in mucosal protection.
KeywordsAnimal models Autoradiography Dextran sulfate sodium Experimental colitis Inflammatory bowel disease Intestinal trefoil factor TFF3
S. Kjellev was supported by a student fellowship from the Danish Ministry for Science, Technology and Innovation. The authors are grateful to the Danish Ministry of Science, Technology and Development and the Danish Research Council for financial support of this study. We thank Grazyna Poulsen, Jette Schousboe, Axel K. Hansen, Bjørg Harryson, Jette Mandelbaum, Steen Kryger, Ann-Christin Løff, and Bodil E. Andersen.
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