Augmented increase in tight junction permeability by luminal stimuli in the non-inflamed ileum of Crohn's disease

• Published in: Gut Vol. 50; no. 3; pp. 307 - 313
• Main Authors: Söderholm, J D, Olaison, G, Peterson, K H, Franzén, L E, Lindmark, T, Wirén, M, Tagesson, C, Sjödahl, R
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.03.2002; BMJ; BMJ Publishing Group LTD; Copyright 2002 by Gut
• Subjects: actin; Actins - analysis; Adult; Aged; Aged, 80 and over; Biological and medical sciences; C10; Clinical Medicine; CLSM; Colonoscopy; confocal laser scanning microscopy; confocal microscopy; Crohn Disease - pathology; Crohn Disease - physiopathology; Crohn's disease; Crohns disease; Decanoic Acids - pharmacology; Diffusion Chambers, Culture; ECP; Electrophysiology; Endoscopy; energy charge potential; Enterocytes - ultrastructure; Experiments; F-actin; Female; filamentous actin; Follow-Up Studies; Gastroenterologi; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Group life insurance; Humans; Ileum - physiopathology; Ileum - ultrastructure; Inflammation; Inflammation and Inflammatory Bowel Disease; inflammatory bowel disease; Intestinal Absorption - physiology; Intestinal Mucosa - physiopathology; Intestinal Mucosa - ultrastructure; Isc; Klinisk medicin; KRB; Krebs-Ringer buffer; Male; Medical and Health Sciences; Medical research; Medical sciences; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Microscopy; Middle Aged; Mitochondria - ultrastructure; Other diseases. Semiology; PDt; Permeability; Permeability - drug effects; Phosphorylation; Proteins; Rodents; short circuit current; Small intestine; sodium caprate; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Studies; TEM; TER; tight junction; tight junctions; Tight Junctions - physiology; Tight Junctions - ultrastructure; transepithelial electrical resistance; transepithelial potential difference; transmission electron microscopy; Human; Contractility; Cell biology; Intestinal wall; Permeability; Experimental study; Ileum; Inflammatory disease; Isolated organ; Crohn disease; Dysfunction; Digestive diseases; Intestinal disease; Cytoskeleton; Tight junction
• ISSN: 0017-5749; 1468-3288; 1468-3288; 1458-3288
• DOI: 10.1136/gut.50.3.307

Background: Crohn's disease is associated with deranged intestinal permeability in vivo, suggesting dysfunction of tight junctions. The luminal contents are important for development of neoinflammation following resection. Regulation of tight junctions by luminal factors has not previously been studied in Crohn's disease. Aims: The aim of the study was to investigate the effects of a luminal stimulus, known to affect tight junctions, on the distal ileum in patients with Crohn's disease. Patients: Surgical specimens from the distal ileum of patients with Crohn's disease (n=12) were studied, and ileal specimens from colon cancer patients (n=13) served as controls. Methods: Mucosal permeability to 51Cr-EDTA and electrical resistance were studied in Ussing chambers during luminal exposure to sodium caprate (a constituent of milk fat, affecting tight junctions) or to buffer only. The mechanisms involved were studied by mucosal ATP levels, and by electron and confocal microscopy. Results: Baseline permeability was the same in non-inflamed ileum of Crohn's disease and controls. Sodium caprate induced a rapid increase in paracellular permeability—that is, increased permeation of 51Cr-EDTA and decreased electrical resistance—which was more pronounced in non-inflamed ileum of Crohn's disease, and electron microscopy showed dilatations within the tight junctions. Moreover, sodium caprate induced disassembly of perijunctional filamentous actin was more pronounced in Crohn's disease mucosa. Mucosal permeability changes were accompanied by mitochondrial swelling and a fall in epithelial ATP content, suggesting uncoupling of oxidative phosphorylation. Conclusions: The tight junctions in the non-inflamed distal ileum of Crohn's disease were more reactive to luminal stimuli, possibly mediated via disturbed cytoskeletal contractility. This could contribute to the development of mucosal neoinflammation in Crohn's disease.