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 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.
['van der Giessen|Janine|J|0000-0002-7265-6768', 'van der Woude|C Janneke|CJ|', 'Peppelenbosch|Maikel P|MP|0000-0001-9112-6028', 'Fuhler|Gwenny M|GM|']
D002460:Cell Line D016207:Cytokines D000091342:Endoplasmic Reticulum Chaperone BiP D059865:Endoplasmic Reticulum Stress D004847:Epithelial Cells D004967:Estrogens D012739:Gonadal Steroid Hormones D006801:Humans D018836:Inflammation Mediators D015212:Inflammatory Bowel Diseases D007413:Intestinal Mucosa D011374:Progesterone D019108:Tight Junctions D014945:Wound Healing
sex hormones inflammatory bowel disease estrogen progesterone pregnancy, epithelial barrier