Department of Gastroenterology and Hepatology, Erasmus Medical Center, 3015CE Rotterdam, The Netherlands.
Cells. 2019 Mar 19;8(3):261. doi: 10.3390/cells8030261.
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.
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.
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.
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.
妊娠通常被描述为一种免疫耐受状态，并且已经提出妊娠对炎症性肠病（IBD）具有疾病调节作用。雌激素和孕激素对肠上皮屏障的直接作用尚未得到充分探索。我们研究了这些妊娠激素对屏障细胞及其功能的直接影响。
我们使用了 IBD 患者来源的炎症类器官模型和 2D 细胞系模型。通过测量跨上皮电阻来分析上皮屏障功能；通过划痕实验测定伤口闭合；通过 MTT 测定法测定细胞活力。通过酶联免疫吸附试验测定促炎细胞因子的产生。通过 Western blot 分析内质网（ER）应激标志物 GRP78、CHOP 和 p-IRE1 来研究 ER 应激诱导的分子调节。
孕激素和雌激素通过上调紧密连接蛋白来改善肠上皮细胞的伤口愈合和上皮屏障功能。此外，这些性激素可显著减轻 ER 应激并减少肠上皮模型中促炎细胞因子的产生。
我们的研究表明，雌激素和孕激素可通过积极调节肠上皮衬里来减轻 ER 应激、减少促炎细胞因子的产生、刺激伤口愈合并增加上皮细胞的屏障功能。综上所述，这些数据表明妊娠激素可通过积极调节肠上皮衬里对疾病活动产生有益影响。
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