The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn’s Disease but Not Ulcerative Colitis Patients
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 colon...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/3/811 |
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| author | Young Su Park Sang Bum Kang Ronald R. Marchelletta Harrison M. Penrose Roos Ruiter-Visser Barbara Jung Michael J. Docherty Brigid S. Boland William J. Sandborn Declan F. McCole |
| author_facet | Young Su Park Sang Bum Kang Ronald R. Marchelletta Harrison M. Penrose Roos Ruiter-Visser Barbara Jung Michael J. Docherty Brigid S. Boland William J. Sandborn Declan F. McCole |
| author_sort | Young Su Park |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T06:02:10Z |
| format | Article |
| id | doaj.art-5f068f2b880b4b1ab6c054eb34c860c1 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T06:02:10Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-5f068f2b880b4b1ab6c054eb34c860c12023-11-17T13:14:43ZengMDPI AGPharmaceutics1999-49232023-03-0115381110.3390/pharmaceutics15030811The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn’s Disease but Not Ulcerative Colitis PatientsYoung Su Park0Sang Bum Kang1Ronald R. Marchelletta2Harrison M. Penrose3Roos Ruiter-Visser4Barbara Jung5Michael J. Docherty6Brigid S. Boland7William J. Sandborn8Declan F. McCole9Division of Gastroenterology, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADivision of Gastroenterology, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADivision of Gastroenterology, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADivision of Gastroenterology, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADivision of Gastroenterology, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADivision of Gastroenterology, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADivision of Gastroenterology, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADivision of Gastroenterology, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADivision of Gastroenterology, School of Medicine, University of California San Diego, La Jolla, CA 92093, USADivision of Biomedical Sciences, School of Medicine, University of California, Riverside, 307 SOM Research Building, 900 University Ave, Riverside, CA 92521, USAThe 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.https://www.mdpi.com/1999-4923/15/3/811chloride secretionepithelialinflammatory bowel diseaseion transportoccludinpermeability |
| spellingShingle | Young Su Park Sang Bum Kang Ronald R. Marchelletta Harrison M. Penrose Roos Ruiter-Visser Barbara Jung Michael J. Docherty Brigid S. Boland William J. Sandborn Declan F. McCole The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn’s Disease but Not Ulcerative Colitis Patients Pharmaceutics chloride secretion epithelial inflammatory bowel disease ion transport occludin permeability |
| title | The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn’s Disease but Not Ulcerative Colitis Patients |
| title_full | The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn’s Disease but Not Ulcerative Colitis Patients |
| title_fullStr | The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn’s Disease but Not Ulcerative Colitis Patients |
| title_full_unstemmed | The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn’s Disease but Not Ulcerative Colitis Patients |
| title_short | The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn’s Disease but Not Ulcerative Colitis Patients |
| title_sort | clc 2 chloride channel activator lubiprostone improves intestinal barrier function in biopsies from crohn s disease but not ulcerative colitis patients |
| topic | chloride secretion epithelial inflammatory bowel disease ion transport occludin permeability |
| url | https://www.mdpi.com/1999-4923/15/3/811 |
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