Increased sensitivity to dextran sodium sulfate colitis in IRE1β-deficient mice
Top Cited Papers
Open Access
- 1 March 2001
- journal article
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 107 (5) , 585-593
- https://doi.org/10.1172/jci11476
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.Keywords
This publication has 61 references indexed in Scilit:
- Recognition of Stress-Induced MHC Molecules by Intestinal Epithelial γδ T CellsScience, 1998
- Reciprocal IFN-γ and TGF-β responses regulate the occurrence of mucosal inflammationImmunology Today, 1997
- A Novel Mechanism for Regulating Activity of a Transcription Factor That Controls the Unfolded Protein ResponseCell, 1996
- The Trefoil Peptide FamilyAnnual Review of Physiology, 1996
- Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses.Journal of Clinical Investigation, 1996
- Ricin Cytotoxicity Is Sensitive to Recycling between the Endoplasmic Reticulum and the Golgi ComplexJournal of Biological Chemistry, 1995
- A transmembrane protein with a cdc 2+ CDC 28 - related kinase activity is required for signaling from the ER to the nucleusPublished by Elsevier ,1993
- Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinaseCell, 1993
- Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogeneCell, 1991
- Inhibition of glycosylation by corynetoxin, the causative agent of annual ryegrass toxicity: A comparison with tunicamycinChemico-Biological Interactions, 1983