Increased intestinal permeability and tight junction disruption by altered expression and localization of occludin in a murine graft versus host disease model
<p>Abstract</p> <p>Background</p> <p>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 bl...
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doaj-e7a7c1bb1de84768b52532d1a36839c12020-11-25T03:44:27ZengBMCBMC Gastroenterology1471-230X2011-10-0111110910.1186/1471-230X-11-109Increased intestinal permeability and tight junction disruption by altered expression and localization of occludin in a murine graft versus host disease modelRosenstiel PhilipBewig BurkhardHampe JochenHäsler RobertEllrichmann MarkKruse Marie-LuiseStüber EckhardLange-Grumfeld JuliaNoth RainerSchreiber StefanArlt Alexander<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p> http://www.biomedcentral.com/1471-230X/11/109 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rosenstiel Philip Bewig Burkhard Hampe Jochen Häsler Robert Ellrichmann Mark Kruse Marie-Luise Stüber Eckhard Lange-Grumfeld Julia Noth Rainer Schreiber Stefan Arlt Alexander |
spellingShingle |
Rosenstiel Philip Bewig Burkhard Hampe Jochen Häsler Robert Ellrichmann Mark Kruse Marie-Luise Stüber Eckhard Lange-Grumfeld Julia Noth Rainer Schreiber Stefan Arlt Alexander Increased intestinal permeability and tight junction disruption by altered expression and localization of occludin in a murine graft versus host disease model BMC Gastroenterology |
author_facet |
Rosenstiel Philip Bewig Burkhard Hampe Jochen Häsler Robert Ellrichmann Mark Kruse Marie-Luise Stüber Eckhard Lange-Grumfeld Julia Noth Rainer Schreiber Stefan Arlt Alexander |
author_sort |
Rosenstiel Philip |
title |
Increased intestinal permeability and tight junction disruption by altered expression and localization of occludin in a murine graft versus host disease model |
title_short |
Increased intestinal permeability and tight junction disruption by altered expression and localization of occludin in a murine graft versus host disease model |
title_full |
Increased intestinal permeability and tight junction disruption by altered expression and localization of occludin in a murine graft versus host disease model |
title_fullStr |
Increased intestinal permeability and tight junction disruption by altered expression and localization of occludin in a murine graft versus host disease model |
title_full_unstemmed |
Increased intestinal permeability and tight junction disruption by altered expression and localization of occludin in a murine graft versus host disease model |
title_sort |
increased intestinal permeability and tight junction disruption by altered expression and localization of occludin in a murine graft versus host disease model |
publisher |
BMC |
series |
BMC Gastroenterology |
issn |
1471-230X |
publishDate |
2011-10-01 |
description |
<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p> |
url |
http://www.biomedcentral.com/1471-230X/11/109 |
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