白介素-1β诱导尾型同源盒转录因子2异位表达在胃黏膜肠上皮化生中的意义

Significance of IL-1β-induced ectopic expression of CDX2 in the intestinal metaplasia of gastric epithelium

目的 探讨白介素（IL）-1β对人胃黏膜上皮细胞尾型同源盒转录因子2（CDX2）表达的调控及其在胃黏膜肠上皮化生中的作用.方法 用不同浓度IL-1β刺激人胃黏膜上皮GES-1细胞,采用实时荧光定量PCR法、免疫细胞化学染色法及免疫印迹方法,在不同时间点检测CDX2 mRNA和蛋白表达水平.使用NF-κB抑制剂二硫代氨基甲酸吡咯烷（PDTC）预处理GES-1细胞,观察PDTC对IL-1β诱导的CDX2 mRNA和蛋白表达的影响.电镜观察IL-1β长期刺激下GES-1细胞超微结构的改变.结果 IL-1β可以诱导人胃黏膜上皮细胞上调CDX2 mRNA的表达.予1μg/LIL-1β刺激后,GES-1细胞CDX2 mRNA和蛋白表达水平分别为0.0749±0.0021和0.56±0.04;加入PDTC后,CDX2 mRNA和蛋白表达水平分别为0.0006±0.0002和0.40±0.06;差异均有统计学意义（均P＜0.05）.IL-1β长期刺激后,GES-1细胞表面会长出很多较长的微绒毛,同时细胞质内的分泌小泡也相应增加,胃上皮细胞开始出现肠上皮细胞的特征.结论 IL-1β能够通过NF-κB通路促进人胃黏膜上皮细胞CDX2 mRNA和蛋白表达上调,在胃黏膜肠上皮化生中发挥重要作用.

Objective To evaluate the effect of IL-lβ on the expression of CDX2 in human gastric epithelial cell line CES-1 and its role in the intestinal metaplasia. Methods GES-1 cells were treated with IL-ip in different concentrations and the expressions of CDX2 mRNA and protein were detected by real-time PCR, immunocytochemistry and Western blot at different time points. GES-1 cells were then pre-treated with NF-KB pathway inhibitor PDTC, and the expression of CDX2 mRNA and protein induced by IL-1β were detected. The cell ultra-structure of GES-1 cells was observed by electronic microscope after GES-1 being treated with IL-1β for 25 days. Results Levels of CDX2 mRNA and protein were 0.0749±0.0021 and 0.56±0.04 in the cells treated with 1 μg/L IL-1β （P〈 0.05）. After pre-treatment with PDTC, levels of CDX2 mRNA and protein were 0.0006±0.0002 and 0.40 ±0.06 （P〈0.05）. Some changes in the cell ultra-structure of GES-1 were found by electronic microscope when GES-1 was treated with IL-1β for 25 days. Conclusion IL-1β can stimulate CDX2 mRNA and protein expression in GES-1 cells through the NF-KB signal pathway, indicating that IL-1β plays an important role in the intestinal metaplasia.