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Intestinal secretory cell ER stress and inflammation


McGuckin, MA and Eri, RD and Das, I and Lourie, R and Florin, TH, Intestinal secretory cell ER stress and inflammation, Biochemical Society Transactions, 39, (4) pp. 1081-1085. ISSN 0300-5127 (2011) [Refereed Article]

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Copyright 2011 Biochemical Society

DOI: doi:10.1042/BST0391081


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. This model 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 is most severe in the distal colon. Inflammation involves TH1, TH2 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.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Genetic immunology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Eri, RD (Associate Professor Raj Eri)
ID Code:71703
Year Published:2011
Web of Science® Times Cited:32
Deposited By:Health Sciences A
Deposited On:2011-08-02
Last Modified:2017-11-07
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