Intestinal secretory cell ER stress and inflammation

McGuckin, Michael A., Eri, Rajaraman D., Das, Indrajit, Lourie, Rohan and Florin, Timothy H. (2011) Intestinal secretory cell ER stress and inflammation. Biochemical Society Transactions, 39 4: 1081-1085. doi:10.1042/BST0391081

Author McGuckin, Michael A.
Eri, Rajaraman D.
Das, Indrajit
Lourie, Rohan
Florin, Timothy H.
Title Intestinal secretory cell ER stress and inflammation
Journal name Biochemical Society Transactions   Check publisher's open access policy
ISSN 0300-5127
Publication date 2011-08
Sub-type Article (original research)
DOI 10.1042/BST0391081
Open Access Status
Volume 39
Issue 4
Start page 1081
End page 1085
Total pages 5
Place of publication London, United Kingdom
Publisher Portland Press
Collection year 2012
Language eng
Formatted abstract
Data from animal models and human inflammatory bowel diseases have implicated the ER (endoplasmic reticulum) stress pathway in intestinal inflammation. We have characterized the development of inflammation in Winnie mice in which ER stress arises due to a single missense mutation in the MUC2 mucin produced by intestinal goblet cells. Thismodel has allowed us to explore the genesis of inflammation ensuing from a single gene polymorphism affecting secretory cells. In these mice, a proportion of MUC2 misfolds during biosynthesis, leading to ER stress and activation of the unfolded protein response. Winnie mice develop spontaneous complex progressive inflammation that ismost severe in the distal colon. Inflammation involves TH1, T H2 and TH17 T-cells, with a progressive development of a TH17-dominated response, but also involves innate immunity, in a pattern not dissimilar to human colitis. Experimental inhibition of tolerance in this model severely exacerbates colitis, demonstrating active effective suppression of inflammation. Even though the misfolding of MUC2 is a consequence of an inherited mutation, as inflammation develops, the molecular markers of ER stress increase further and goblet cell pathology becomes worse, suggesting that inflammation itself exacerbates ER stress.
Keyword Endoplasmic reticulum stress (ER stress)
Goblet cell
Inflammatory bowel disease (IBD)
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
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