Increased intestinal permeability and tight junction disruption by altered expression and localization of occludin in a murine graft versus host disease model

BMC Gastroenterology

Research Article

Rainer Noth¹  Marie-Luise Kruse¹  Eckhard Stüber¹  Burkhard Bewig¹  Mark Ellrichmann¹  Jochen Hampe¹  Alexander Arlt¹  Julia Lange-Grumfeld¹  Stefan Schreiber²  Robert Häsler³  Philip Rosenstiel³ 

[1] Department of Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, 24105, Kiel, Germany;Department of Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, 24105, Kiel, Germany;Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, 24105, Kiel, Germany;Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, 24105, Kiel, Germany;

关键词: Tight Junction;    Hematopoietic Stem Cell Transplantation;    Lactulose;    Intestinal Permeability;    Graft Versus Host Disease;   

DOI  :  10.1186/1471-230X-11-109

 received in 2011-05-17, accepted in 2011-10-06,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundHematopoietic stem cell transplantation is increasingly performed for hematologic diseases. As a major side effect, acute graft versus host disease (GvHD) with serious gastrointestinal symptoms including diarrhea, gastrointestinal bleeding and high mortality can be observed. Because surveillance and biopsies of human gastrointestinal GvHD are difficult to perform, rare information of the alterations of the gastrointestinal barrier exists resulting in a need for systematic animal models.MethodsTo investigate the effects of GvHD on the intestinal barrier of the small intestine we utilized an established acute semi allogenic GvHD in C57BL/6 and B6D2F1 mice.ResultsBy assessing the differential uptake of lactulose and mannitol in the jejunum, we observed an increased paracellular permeability as a likely mechanism for disturbed intestinal barrier function. Electron microscopy, immunohistochemistry and PCR analysis indicated profound changes of the tight-junction complex, characterized by downregulation of the tight junction protein occludin without any changes in ZO-1. Furthermore TNF-α expression was significantly upregulated.ConclusionsThis analysis in a murine model of GvHD of the small intestine demonstrates serious impairment of intestinal barrier function in the jejunum, with an increased permeability and morphological changes through downregulation and localization shift of the tight junction protein occludin.

【 授权许可】

Unknown   
© Noth et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.