The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn’s Disease but Not Ulcerative Colitis Patients

• Published in: Pharmaceutics Vol. 15; no. 3; p. 811
• Main Authors: Park, Young Su, Kang, Sang Bum, Marchelletta, Ronald R., Penrose, Harrison M., Ruiter-Visser, Roos, Jung, Barbara, Docherty, Michael J., Boland, Brigid S., Sandborn, William J., McCole, Declan F.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2023; MDPI
• Subjects: Biopsy; Chloride; chloride secretion; Constipation; Crohn's disease; Cystic fibrosis; Dosage and administration; Drug therapy; epithelial; Fatty acids; Inflammatory bowel disease; ion transport; Ions; Irritable bowel syndrome; Localization; Lubiprostone; occludin; Patients; Permeability; Proteins; Remission (Medicine); Testing; Ulcerative colitis; United States; occludin; permeability; epithelial; chloride secretion; ion transport; inflammatory bowel disease; tight junction
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics15030811

The prostone analog, lubiprostone, is approved to manage constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in animal models of colitis. The aim of this study was to determine if lubiprostone improves barrier properties in isolated colonic biopsies from Crohn’s disease (CD) and ulcerative colitis (UC) patients. Sigmoid colon biopsies from healthy subjects, CD and UC patients in remission, and CD patients with active disease were mounted in Ussing chambers. Tissues were treated with lubiprostone or vehicle to determine the effects on transepithelial electrical resistance (TER), FITC-dextran 4kD (FD4) permeability, and electrogenic ion transport responses to forskolin and carbachol. Localization of the tight junction protein, occludin, was determined by immunofluorescence. Lubiprostone significantly increased ion transport across control, CD and UC remission biopsies but not active CD. Lubiprostone selectively improved TER in both CD remission and active disease biopsies but not in control or UC biopsies. The improved TER was associated with increased membrane localization of occludin. Lubiprostone selectively improved barrier properties of biopsies from CD patients vs. UC and independent of an ion transport response. These data indicate that lubiprostone has potential efficacy in improving mucosal integrity in Crohn’s disease.