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A Direct Effect of Sex Hormones on Epithelial Barrier Function in Inflammatory Bowel Disease Models

Background: Pregnancy is often described as an immune-tolerant state, and a disease modulatory role for pregnancy on inflammatory bowel disease (IBD) has been suggested. The direct effect of estrogen and progesterone on the intestinal epithelial barrier is underexplored. We investigated the direct c...

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Autores principales: van der Giessen, Janine, van der Woude, C. Janneke, Peppelenbosch, Maikel P., Fuhler, Gwenny M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468635/
https://www.ncbi.nlm.nih.gov/pubmed/30893871
http://dx.doi.org/10.3390/cells8030261
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author van der Giessen, Janine
van der Woude, C. Janneke
Peppelenbosch, Maikel P.
Fuhler, Gwenny M.
author_facet van der Giessen, Janine
van der Woude, C. Janneke
Peppelenbosch, Maikel P.
Fuhler, Gwenny M.
author_sort van der Giessen, Janine
collection PubMed
description Background: Pregnancy is often described as an immune-tolerant state, and a disease modulatory role for pregnancy on inflammatory bowel disease (IBD) has been suggested. The direct effect of estrogen and progesterone on the intestinal epithelial barrier is underexplored. We investigated the direct consequences of these pregnancy hormones on barrier cells and their function. Methods: We used IBD patient-derived inflammatory organoid models and 2D cell lines models. Epithelial barrier function was analyzed by measuring transepithelial electrical resistance; wound closure was determined by scratch assay; and cell viability was measured by MTT assays. Pro-inflammatory cytokine production was determined by enzyme-linked immunosorbent assays. Molecular modulation of endoplasmic reticulum (ER) stress induced by tunicamycin was studied by western blot analysis of the ER stress markers GRP78, CHOP and p-IRE1. Results: Progesterone and estrogen improved wound healing and epithelial barrier function in intestinal epithelial cells via upregulation of tight junction proteins. Furthermore, these sex hormones significantly reduced ER-stress and reduce pro-inflammatory cytokine production in intestinal epithelial models. Conclusion: Our study shows that estrogen and progesterone alleviate ER stress, decrease pro-inflammatory cytokine production, stimulate wound healing, and increase barrier function of epithelial cells. Combined, these data suggest that pregnancy hormones can have beneficial effects on disease activity by positively modulating the intestinal epithelial lining.
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spelling pubmed-64686352019-04-23 A Direct Effect of Sex Hormones on Epithelial Barrier Function in Inflammatory Bowel Disease Models van der Giessen, Janine van der Woude, C. Janneke Peppelenbosch, Maikel P. Fuhler, Gwenny M. Cells Article Background: Pregnancy is often described as an immune-tolerant state, and a disease modulatory role for pregnancy on inflammatory bowel disease (IBD) has been suggested. The direct effect of estrogen and progesterone on the intestinal epithelial barrier is underexplored. We investigated the direct consequences of these pregnancy hormones on barrier cells and their function. Methods: We used IBD patient-derived inflammatory organoid models and 2D cell lines models. Epithelial barrier function was analyzed by measuring transepithelial electrical resistance; wound closure was determined by scratch assay; and cell viability was measured by MTT assays. Pro-inflammatory cytokine production was determined by enzyme-linked immunosorbent assays. Molecular modulation of endoplasmic reticulum (ER) stress induced by tunicamycin was studied by western blot analysis of the ER stress markers GRP78, CHOP and p-IRE1. Results: Progesterone and estrogen improved wound healing and epithelial barrier function in intestinal epithelial cells via upregulation of tight junction proteins. Furthermore, these sex hormones significantly reduced ER-stress and reduce pro-inflammatory cytokine production in intestinal epithelial models. Conclusion: Our study shows that estrogen and progesterone alleviate ER stress, decrease pro-inflammatory cytokine production, stimulate wound healing, and increase barrier function of epithelial cells. Combined, these data suggest that pregnancy hormones can have beneficial effects on disease activity by positively modulating the intestinal epithelial lining. MDPI 2019-03-19 /pmc/articles/PMC6468635/ /pubmed/30893871 http://dx.doi.org/10.3390/cells8030261 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
van der Giessen, Janine
van der Woude, C. Janneke
Peppelenbosch, Maikel P.
Fuhler, Gwenny M.
A Direct Effect of Sex Hormones on Epithelial Barrier Function in Inflammatory Bowel Disease Models
title A Direct Effect of Sex Hormones on Epithelial Barrier Function in Inflammatory Bowel Disease Models
title_full A Direct Effect of Sex Hormones on Epithelial Barrier Function in Inflammatory Bowel Disease Models
title_fullStr A Direct Effect of Sex Hormones on Epithelial Barrier Function in Inflammatory Bowel Disease Models
title_full_unstemmed A Direct Effect of Sex Hormones on Epithelial Barrier Function in Inflammatory Bowel Disease Models
title_short A Direct Effect of Sex Hormones on Epithelial Barrier Function in Inflammatory Bowel Disease Models
title_sort direct effect of sex hormones on epithelial barrier function in inflammatory bowel disease models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468635/
https://www.ncbi.nlm.nih.gov/pubmed/30893871
http://dx.doi.org/10.3390/cells8030261
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