Department of Pediatric, Affiliated Shengjing Hospital, China Medical University, Shenyang, 110004, Liaoning, China.
Inflammation. 2012 Feb;35(1):308-15. doi: 10.1007/s10753-011-9320-x.
Intestinal barrier dysfunction plays an important role in the pathogenesis of inflammatory bowel disease (IBD). To evaluate the effect of intestinal trefoil factor (ITF) on increased intestinal permeability and its association with tight junction proteins, an in vitro intestinal epithelia barrier model was established with Caco-2 cells and treated with platelet-activating factor (PAF). We found that exposing cells to 0.3 M ITF (30 min before or 30 min after PAF treatment) attenuated the PAF-induced changes in transepithelial electrical resistance and Lucifer yellow flux. A quantitative RT-PCR and western blot analysis revealed that ITF suppressed PAF-induced downregulation of tight junction proteins claudin-1 and ZO-1 expression; furthermore, an abnormal localization and distribution of these proteins was inhibited, as assessed by immunofluorescence staining. These results suggest that ITF decreases mucosal permeability and shows potential as a therapy for treating IBD.
肠屏障功能障碍在炎症性肠病 (IBD) 的发病机制中起重要作用。为了评估三叶因子 (ITF) 对增加的肠通透性的影响及其与紧密连接蛋白的关系,我们使用 Caco-2 细胞建立了体外肠上皮屏障模型,并用血小板激活因子 (PAF) 处理细胞。我们发现,在 PAF 处理前 30 分钟或处理后 30 分钟用 0.3 M ITF 孵育细胞可减轻 PAF 诱导的跨上皮电阻和 Lucifer yellow 通量的变化。定量 RT-PCR 和 Western blot 分析表明,ITF 抑制了 PAF 诱导的紧密连接蛋白 claudin-1 和 ZO-1 表达的下调;此外,通过免疫荧光染色抑制了这些蛋白的异常定位和分布。这些结果表明,ITF 可降低黏膜通透性,具有治疗 IBD 的潜力。