학술논문
Subepithelial Serotonin Reduces Small Intestinal Epithelial Cell Tightness via Reduction of Occluding Expression
ORIGINAL ARTICLE:BASIC & TRANSLATIONAL
ORIGINAL ARTICLE:BASIC & TRANSLATIONAL
Document Type
Report
Author
Source
The Turkish Journal of Gastroenterology. January 2022, Vol. 33 Issue 1, p74, 6 p.
Subject
Language
English
ISSN
1300-4948
Abstract
INTRODUCTION About 5-20% of people in the world have been reported to be affected by irritable bowel syndrome (IBS). (1,2) Particularly in Asia, the incidence of IBS has recently been [...]
Background: The precise pathogenesis of irritable bowel syndrome (IBS) remains unresolved; however, recent studies have reported that patients with diarrhea-predominant IBS exhibit an increased small intestinal permeability and increased number of enterochromaffin cells containing high 5-hydroxytryptamine (5HT; serotonin) levels. In this study, we investigated whether 5HT has the potential to modulate small intestinal epithelial cell permeability, focusing on tight junction-associated proteins. Methods: The differentiated Caco-2 cell monolayer on porous filters (Millicell) was used. Then, 5HT was added to the lower Millicell compartment for 7 days. Intestinal epithelial cell permeability was assessed by measuring the flux of paracellular permeability markers. We further assessed the expression of occludin in the 5HT-stimulated Caco-2 monolayer. Results: We found that 5HT did not affect the viability of Caco-2 cells at concentrations up to 100 [micro]M during the experimental period. Administration of 5HT to the basal side of Caco-2 cells increased the flux of [.sup.3]H-labeled mannitol (182 Da) but did not increase that of FITC-dextran (4000 Da). Among the tight junction proteins, the expression of occludin was specifically decreased by stimulation with 5HT at a concentration of 100 [micro]M. Conclusion: In conclusion, excessive 5HT in the basal side increased the permeability of intestinal epithelial cells via reduction of occludin expression. Keywords: Irritable bowel syndrome, serotonin, tight junction, epithelial cell, permeability
Background: The precise pathogenesis of irritable bowel syndrome (IBS) remains unresolved; however, recent studies have reported that patients with diarrhea-predominant IBS exhibit an increased small intestinal permeability and increased number of enterochromaffin cells containing high 5-hydroxytryptamine (5HT; serotonin) levels. In this study, we investigated whether 5HT has the potential to modulate small intestinal epithelial cell permeability, focusing on tight junction-associated proteins. Methods: The differentiated Caco-2 cell monolayer on porous filters (Millicell) was used. Then, 5HT was added to the lower Millicell compartment for 7 days. Intestinal epithelial cell permeability was assessed by measuring the flux of paracellular permeability markers. We further assessed the expression of occludin in the 5HT-stimulated Caco-2 monolayer. Results: We found that 5HT did not affect the viability of Caco-2 cells at concentrations up to 100 [micro]M during the experimental period. Administration of 5HT to the basal side of Caco-2 cells increased the flux of [.sup.3]H-labeled mannitol (182 Da) but did not increase that of FITC-dextran (4000 Da). Among the tight junction proteins, the expression of occludin was specifically decreased by stimulation with 5HT at a concentration of 100 [micro]M. Conclusion: In conclusion, excessive 5HT in the basal side increased the permeability of intestinal epithelial cells via reduction of occludin expression. Keywords: Irritable bowel syndrome, serotonin, tight junction, epithelial cell, permeability