Zhou Zejun, Zhang Lumin, Ding Miao, Luo Zhenwu, Yuan Shao, Bansal Meena B, Gilkeson Gary, Lang Ren, Jiang Wei
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Clin Immunol. 2017 Oct;183:174-180. doi: 10.1016/j.clim.2017.08.019. Epub 2017 Sep 1.
Females have a higher prevalence of most autoimmune diseases; however, the mechanism is unknown. In this study, we examined the expression of tight junction protein zonula occludens 1 (ZO-1) and estrogen receptor (ER)-α/β in human primary gut tissues by immunohistochemistry, immunofluorescence and qPCR. The expression of ZO-1 and ER-β but not ER-α was present in both male and female gut tissues. There was no sex difference in ER-β expression, but ZO-1 expression was decreased in females compared to males. In vitro, estrogen treatment decreased ZO-1 mRNA and protein expression, ZO-1 promoter activity, IL-6 production, and NF-κB activation in human primary gut tissues or the Caco-2 cells, but increased the ER-β expression in Caco-2 cells. Consistently, plasma IL-6 levels in females were reduced relative to males in vivo. Our finding indicates that estrogen may play a role in gut tight junction expression and permeability.
大多数自身免疫性疾病在女性中的患病率更高；然而，其机制尚不清楚。在本研究中，我们通过免疫组织化学、免疫荧光和定量聚合酶链反应检测了人原发性肠道组织中紧密连接蛋白闭合蛋白1（ZO-1）和雌激素受体（ER）-α/β的表达。ZO-1和ER-β而非ER-α在男性和女性肠道组织中均有表达。ER-β表达无性别差异，但与男性相比，女性的ZO-1表达降低。在体外，雌激素处理降低了人原发性肠道组织或Caco-2细胞中ZO-1 mRNA和蛋白表达、ZO-1启动子活性、白细胞介素-6（IL-6）产生和核因子-κB（NF-κB）激活，但增加了Caco-2细胞中ER-β表达。同样，在体内，女性血浆IL-6水平相对于男性降低。我们的研究结果表明，雌激素可能在肠道紧密连接表达和通透性中发挥作用。
