Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan,
Pharmacology. 2020;105(1-2):102-108. doi: 10.1159/000503054. Epub 2019 Sep 19.
Lubiprostone, a chloride channel activator, is said to reduce epithelial permeability. However, whether lubiprostone has a direct effect on the epithelial barrier function and how it modulates the intestinal barrier function remain unknown. Therefore, the effects of lubiprostone on intestinal barrier function were evaluated in vitro.
Caco-2 cells were used to assess the intestinal barrier function. To examine the expression of claudins, immunoblotting was performed with specific antibodies. The effects of lubiprostone on cytokines (IFNγ, IL-6, and IL-1β) and aspirin-induced epithelial barrier disruption were assessed by transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC) labeled-dextran permeability.
IFNγ, IL-6, IL-1β, and aspirin significantly decreased TEER and increased epithelial permeability. Lubiprostone significantly improved the IFNγ-induced decrease in TEER in a dose-dependent manner. Lubiprostone significantly reduced the IFNγ-induced increase in FITC labeled-dextran permeability. The changes induced by IL-6, IL-1β, and aspirin were not affected by lubiprostone. The expression of claudin-1, but not claudin-3, claudin-4, occludin, and ZO-1 was significantly increased by lubiprostone.
Lubiprostone significantly improved the IFNγ-induced decrease in TEER and increase in FITC labeled-dextran permeability. Lubiprostone increased the expression of claudin-1, and this increase may be related to the effect of lubiprostone on the epithelial barrier function.
Lubiprostone 是一种氯离子通道激活剂，据称可降低上皮细胞通透性。然而，Lubiprostone 是否对上皮屏障功能有直接影响以及它如何调节肠道屏障功能尚不清楚。因此，本研究评估了 Lubiprostone 在体外对肠道屏障功能的影响。
使用 Caco-2 细胞评估肠道屏障功能。使用特异性抗体进行免疫印迹以检测 Claudin 的表达。通过跨上皮电阻（TEER）和荧光素异硫氰酸酯（FITC）标记的葡聚糖通透性评估 Lubiprostone 对细胞因子（IFNγ、IL-6 和 IL-1β）和阿司匹林诱导的上皮屏障破坏的影响。
IFNγ、IL-6、IL-1β 和阿司匹林显著降低了 TEER 并增加了上皮通透性。Lubiprostone 呈剂量依赖性显著改善 IFNγ 诱导的 TEER 降低。Lubiprostone 显著降低了 IFNγ 诱导的 FITC 标记的葡聚糖通透性增加。IL-6、IL-1β 和阿司匹林引起的变化不受 Lubiprostone 影响。Lubiprostone 显著增加 Claudin-1 的表达，但 Claudin-3、Claudin-4、occludin 和 ZO-1 的表达没有变化。
Lubiprostone 显著改善了 IFNγ 诱导的 TEER 降低和 FITC 标记的葡聚糖通透性增加。Lubiprostone 增加了 Claudin-1 的表达，这种增加可能与 Lubiprostone 对上皮屏障功能的影响有关。
