Altered permeability in inflammatory bowel disease: pathophysiology and clinical implications
- 1 July 2007
- journal article
- review article
- Published by Wolters Kluwer Health in Current Opinion in Gastroenterology
- Vol. 23 (4), 379-383
- https://doi.org/10.1097/mog.0b013e32816aa392
Abstract
To present the mechanisms behind barrier disturbance in inflammatory bowel disease and their functional consequences. A reduction in tight junction strands, strand breaks and alteration of tight junction protein content and composition characterize Crohn's disease. In ulcerative colitis, epithelial leaks appear early as a result of microerosions, upregulated epithelial apoptosis and tight junction protein changes with pronounced increases in claudin-2. T-helper type 1 cytokine effects by interferon-gamma and tumour necrosis factor alpha are important for epithelial damage in Crohn's disease. Interleukin-13 is the key effector cytokine in ulcerative colitis, stimulating epithelial cell apoptosis, and can upregulate claudin-2 expression. Together with interleukin-13-induced epithelial restitution arrest, this may explain why ulcer lesions occur in early stages of ulcerative colitis but are only observed in advanced inflammatory stages in Crohn's disease. Barrier dysfunction in inflammatory bowel disease contributes to diarrhea by a leak flux mechanism and can cause mucosal inflammation secondary to luminal antigen uptake. Barrier abnormalities, such as epithelial tight junction changes and apoptotic leaks, gross mucosal lesions, and epithelial restitution arrest are responsible for these abnormalities and are the result of immune dysregulation. Studying the underlying mechanisms is important in understanding the pathophysiology of inflammatory bowel disease and developing therapeutic strategies.Keywords
This publication has 61 references indexed in Scilit:
- Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's diseaseGut, 2007
- Disrupted Barrier Function through Epithelial Cell ApoptosisAnnals of the New York Academy of Sciences, 2006
- Genetic basis for increased intestinal permeability in families with Crohn's disease: role of CARD15 3020insC mutation?Gut, 2006
- Increased epithelial uptake of protein antigens in the ileum of Crohn's disease mediated by tumour necrosis factorGut, 2004
- Downregulation of epithelial apoptosis and barrier repair in active Crohn's disease by tumour necrosis factor antibody treatmentGut, 2004
- Antigen Transport and Cytoskeletal Characteristics of a Distinct Enterocyte Population in Inflammatory Bowel DiseasesThe American Journal of Pathology, 2004
- Epithelial barrier defects in ulcerative colitis: Characterization and quantification by electrophysiological imagingGastroenterology, 2001
- Permeability of human HT‐29/B6 colonic epithelium as a function of apoptosisThe Journal of Physiology, 2001
- Leaks in the epithelial barrier caused by spontaneous and TNF‐α‐induced single‐cell apoptosisThe FASEB Journal, 2000
- Transepithelial transport processes at the intestinal mucosa in inflammatory bowel diseaseInternational Journal of Colorectal Disease, 1999