The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2022
Subepithelial Serotonin Reduces Small Intestinal Epithelial Cell Tightness via Reduction of Occluding Expression.
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Horie Hideki, Handa Osamu, Naito Yuji, Majima Atsushi, Yasuda-Onozawa Yuriko, Uehara Yukiko, Kamada Kazuhiro, Katada Kazuhiro, Uchiyama Kazuhiko, Ishikawa Takeshi, Takagi Tomohisa, Itoh Yoshito, Shiotani Akiko
Аннотация
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 µM during the experimental period. Administration of 5HT to the basal side of Caco-2 cells increased the flux of 3H-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 µM.
CONCLUSION: In conclusion, excessive 5HT in the basal side increased the permeability of intestinal epithelial cells via reduction of occludin expression.
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 µM during the experimental period. Administration of 5HT to the basal side of Caco-2 cells increased the flux of 3H-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 µM.
CONCLUSION: In conclusion, excessive 5HT in the basal side increased the permeability of intestinal epithelial cells via reduction of occludin expression.