Abstract | 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.
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Authors | Hideki Horie, Osamu Handa, Yuji Naito, Atsushi Majima, Yuriko Yasuda-Onozawa, Yukiko Uehara, Kazuhiro Kamada, Kazuhiro Katada, Kazuhiko Uchiyama, Takeshi Ishikawa, Tomohisa Takagi, Yoshito Itoh, Akiko Shiotani |
Journal | The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology
(Turk J Gastroenterol)
Vol. 33
Issue 1
Pg. 74-79
(01 2022)
ISSN: 2148-5607 [Electronic] Turkey |
PMID | 35040791
(Publication Type: Journal Article)
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Chemical References |
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Topics |
- Caco-2 Cells
- Epithelial Cells
(metabolism)
- Humans
- Intestinal Mucosa
(metabolism)
- Irritable Bowel Syndrome
(metabolism)
- Occludin
(metabolism)
- Serotonin
(metabolism, pharmacology)
- Tight Junctions
(metabolism)
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