[HTML][HTML] Increased intestinal permeability and tight junction disruption by altered expression and localization of occludin in a murine graft versus host disease model
R Noth, J Lange-Grumfeld, E Stüber, ML Kruse… - BMC …, 2011 - Springer
BMC gastroenterology, 2011•Springer
Background 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. Methods To investigate the effects of …
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. Methods To investigate the effects of …
Background
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.
Methods
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.
Results
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.
Conclusions
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.
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