NEW YORK (Reuters Health) - Genes involved in cellular detoxification and defense appear to be downregulated in patients with inflammatory bowel disease (IBD), German researchers report in the July issue of Gut.
“Our study provides clear evidence that intestinal epithelial cells are key players in the development of IBD and that proper mucosa cell homeostasis, including nutrition and detoxification, is very important for physiological gut functions,” lead investigator Dr. Thomas Langmann told Reuters Health.
It is likely that ulcerative colitis and Crohn’s disease are a result of “multiple, interacting factors, including several susceptibility genes, which are expressed in mucosa epithelial cells and immune cells,” Dr. Langmann of the University of Regensburg and colleagues report.
The researchers used DNA microarray analysis and real-time reverse-transcription polymerase chain reaction to examine resected terminal ileum and colonic tissues from patients with ulcerative colitis and Crohn’s disease and from controls.
Overall, the researchers found that in patients with inflammatory bowel disease, 1390 genes were dysregulated in the ileum. Moreover, 2860 genes in the colon also showed consistent differences from controls.
A particular set of genes downregulated in patients with ulcerative colitis was composed of cellular detoxification and defense genes. These, say the investigators, are target genes for the transcription factor pregnane X receptor (PXR).
PXR was “strongly reduced” in patients with ulcerative colitis. This was also true of RNA expression of the transporter ABCB1. However, this was not the case in samples from patients with Crohn’s disease.
The researchers conclude that “dysregulation of xenobiotic metabolism and PXR activity in the gut is likely to contribute to the pathophysiology of ulcerative colitis.”
In a comment to Reuters Health, senior author Dr. Gerd Schmitz added that “based on our data, one could envision a nutraceutical therapy approach for IBD aimed at improving the barrier and defense functions of mucosa cells and thereby to reduce the severe clinical symptoms of IBD.”
Source: Gastroenterology 2004;127:26-40. [ Google search on this article ]
MeSH Headings:Biological Sciences: Biology: Gene Expression Regulation: Genetics: Genetics, Biochemical: Specialty Chemicals and Products: Molecular Biology: Xenobiotics: etiology: Biological Sciences: Chemicals and DrugsCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
