Increased sensitivity to dextran sodium sulfate colitis in IRE1β-deficient mice

Anne Bertolotti, XiaoZhong Wang, Isabel Novoa, Rivka Jungreis, Karni Schlessinger, Judy H. Cho, A. Brian West, David Ron*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

290 Scopus citations

Abstract

The epithelial cells of the gastrointestinal tract are exposed to toxins and infectious agents that can adversely affect protein folding in the endoplasmic reticulum (ER) and cause ER stress. The IRE1 genes are implicated in sensing and responding to ER stress signals. We found that epithelial cells of the gastrointestinal tract express IRE1β, a specific isoform of IRE1. BiP protein, a marker of ER stress, was elevated in the colonic mucosa of IRE1β-/- mice, and, when exposed to dextran sodium sulfate (DSS) to induce inflammatory bowel disease, mutant mice developed colitis 3-5 days earlier than did wild-type or IRE1β+/- mice. The inflammation marker ICAM-1 was also expressed earlier in the colonic mucosa of DSS-treated IRE1β-/- mice, indicating that the mutation had its impact early in the inflammatory, process, before the onset of mucosal ulceration. These findings are consistent with a model whereby perturbations in ER function, which are normally mitigated by the activity of IRE1β, participate in the development of colitis.

Original languageEnglish (US)
Pages (from-to)585-593
Number of pages9
JournalJournal of Clinical Investigation
Volume107
Issue number5
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Medicine(all)

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