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

Authors:
Rainer Noth, Julia Lange-Grumfeld, Eckhard Stüber, Marie-Luise Kruse, Mark Ellrichmann, Robert Häsler, Jochen Hampe, Burkhard Bewig, Philip Rosenstiel, Stefan Schreiber, Alexander Arlt
Year of publication:
2011
Volume:
11
Issue:
-
Issn:
1471-230X
Journal title abbreviated:
BMC GASTROENTEROL
Journal title long:
BMC gastroenterology
Impact factor:
2.212
Abstract: 
This 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.By 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.To 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.Hematopoietic 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.