白介素-1β诱导胃上皮细胞GES-1表达肠道特异性标志物

IL-1β Induces Expression of Intestinal Specific Markers in Cultured Human Gastric Epithelial Cells GES-1

目的观察白细胞介素-1β(IL-1β)对体外培养的人胃黏膜上皮GES-1细胞中肠道特异性标志物尾侧型同源转录因子-1(CDX1)和肠道黏蛋白-2(MUC2)表达的诱导作用,探讨其作用机理。方法通过不同浓度及不同作用时间的IL-1β刺激人胃黏膜上皮GES-1细胞,采用实时定量PCR法检测CDX1mRNA和MUC2mRNA的表达水平;并使用NF-κB抑制剂PDTC预处理GES-1细胞,检测PDTC对IL-1β诱导的CDX1mRNA和MUC2mRNA表达水平的影响。结果正常情况下人胃黏膜上皮GES-1细胞不表达CDX1mRNA和MUC2mRNA,而IL-1β可以诱导GES-1细胞中CDX1mRNA和MUC2mRNA的表达,该作用在一定浓度范围内呈现剂量依赖性(P<0.05);IL-1β作用8h时,CDX1mRNA和MUC2mRNA的表达达到峰值(P<0.05),随后表达逐渐降低。经NF-κB抑制剂PDTC预处理后的GES-1细胞,CDX1mRNA和MUC2mRNA的表达水平明显下降(P<0.05)。结论IL-1β可能通过NF-κB信号通路促进人胃黏膜上皮细胞中CDX1mRNA和MUC2mRNA的表达,在胃黏膜肠上皮化生中发挥作用。

Objective To observed the effect of IL-1β on expression of caudal related homeobox gene 1 （CDX1） mRNA and mucoprotein 2 （MUC2） mRNA in cultured human gastric epithelial cells GES-1, and to investigate the underlying signal transduction pathways. Methods ①GES-1 cell was activated with IL-1β of different con- centrations and time, the expression levels of CDX1 mRNA and MUC2 mRNA were detected by using real-time PCR. ②GES-1 cell was pretreated with PDTC, a NF-κB inhibitor, for 1h prior to the addition of IL-1β, then the expressions of CDX1 mRNA and MUC2 mRNA were measured. Results Both CDX1 mRNA and MUC2 mRNA were not examined in GES-1 cell under normal culture conditions. But they could be induced by IL-1β with a dose- dependent manner in a concentration range （P〈0.05） ; 8 h after treatment with IL-1β, the peak values of the ex- pression levels of CDX1 mRNA and MUC2 mRNA were reached （P〈0.05）, then declined gradually. When pre-incubated with NF-κB inhibitor PDTC, the expression levels of CDX1 mRNA and MUC2 mRNA were significantly decreased （P〈0.05）. Conclusion IL-1β significantly induces the expressions of CDX1 mRNA and MUC2 mRNA in cultured human gastric epithelial cell GES-1 through the NF-κB signal pathway, which indicates that IL-1β plays a role in the process of intestinal metaplasia. [Key words]