Document Detail


Endoplasmic reticulum stress and inflammatory bowel disease.
MedLine Citation:
PMID:  21861319     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Endoplasmic reticulum (ER) stress arises from the accumulation of misfolded or unfolded proteins in the ER and elicits the unfolded protein response (UPR), an adaptive signalling pathway which aims at resolving ER stress. Genetic loci that confer risk for both forms of inflammatory bowel disease (IBD) include genes that are centrally involved in the UPR, including X-box binding protein-1 (XBP1), anterior gradient protein-2 (AGR2) and orosomucoid-1-like 3 (ORMDL3). The intestinal epithelium, in particular mucin-secreting goblet and antimicrobial peptide-secreting Paneth cells appear particularly sensitive towards disturbances of the UPR. Supportive of this view are mice with a genetic deletion of Xbp1 specifically in the intestinal epithelium, which develop spontaneous intestinal inflammation histologically remarkably similar to human IBD. Apart from such primary genetic factors that determine the threshold of tolerable ER stress within the epithelium, secondary factors emanating from the environment might intersect with the UPR as well. These secondary factors might include microbial products, inflammatory mediators per se, hypoxia and glucose deprivation, pharmacological agents, and many others. Interaction of such secondary factors in a genetically susceptible host might provide the basis for intestinal inflammation and might provide a framework to investigate gene-environment interactions in human IBD, whereby a normally homeostatic adaptive response (i.e. the UPR) transforms into a potent pathomechanism of intestinal inflammation in the context of unresolved (i.e. unresolvable) ER stress.
Authors:
Lukas Niederreiter; Arthur Kaser
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Acta gastro-enterologica Belgica     Volume:  74     ISSN:  0001-5644     ISO Abbreviation:  Acta Gastroenterol. Belg.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-08-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0414075     Medline TA:  Acta Gastroenterol Belg     Country:  Belgium    
Other Details:
Languages:  eng     Pagination:  330-3     Citation Subset:  IM    
Affiliation:
Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
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