Helicobacter pylori activates the early growth response 1 protein in gastric epithelial cells
Helicobacter pylori activates the early growth response 1 protein in gastric epithelial cells
复制标题
DOI：
10.1128/iai.72.6.3549-3560.2004
复制
发表时间：
2004-06-01
影响因子：
3.1
通讯作者：
Kelleher, D
中科院分区：
文献类型：
--
作者：
Abdel-Latif, MMM;Windle, HJ;Kelleher, D
早期生长反应1（Egr-1）转录因子被各种刺激快速诱导，并且涉及细胞生长、分化和基因表达的调节。本研究旨在探讨幽门螺杆菌对胃上皮AGS细胞Egr-1及其调控基因表达的影响。用H.幽门刺激的AGS细胞。使用CD 44、ICAM-1和CD 95 L的启动子-报告基因构建体的瞬时转染实验用于表达研究。H. pylori以剂量依赖性方式诱导胃上皮细胞系中Egr-1的表达，具有这类转录因子典型的快速动力学。活检组织的免疫组化研究显示Egr-1在H. pylori阳性的患者比未感染的个体。报告子-启动子转染研究表明，Egr-1的结合是H. pylori诱导的CD 44、ICAM-1和CD 95 L（APO-1/Fas）构建体的转录启动子活性。用反义序列阻断HLA-I可阻止H. pylori诱导的Egr-1和CD 44蛋白表达。MEK 1/2信号级联参与H. pylori介导的Egr-1表达，但p38通路没有。数据表明，H. pylori在体外诱导AGS细胞中Egr-1表达，并且Egr-1蛋白在来自H.幽门阳性的受试者。这些结果表明，H.幽门相关Egr-1表达可能在H. pylori引起的病理学。
The early growth response 1 (Egr-1) transcription factor is rapidly induced by various stimuli and is implicated in the regulation of cell growth, differentiation, and gene expression. The aim of this study was to examine the effect of Helicobacter pylori on the expression of Egr-1 and Egr-1-regulated genes in gastric epithelial AGS cells. Egr-1 expression was assayed by immunoblotting and electrophoretic mobility shift assays using H. pylori-stimulated AGS cells. Transient transfection experiments with promoter-reporter constructs of CD44, ICAM-1, and CD95L were used for expression studies. H. pylori induced the expression of Egr-1 in gastric epithelial cell lines in a dose-dependent manner, with the rapid kinetics that are typical of this class of transcription factors. Immunohistochemical studies of biopsies revealed that Egr-1 expression is more abundant in H. pylori-positive patients than in uninfected individuals. Reporter-promoter transfection studies indicated that Egr-1 binding is required for the H. pylori-induced transcriptional promoter activity of the CD44, ICAM-1, and CD95L (APO-1/Fas) constructs. The blocking of egr-1 with an antisense sequence prevented H. pylori-induced Egr-1 and CD44 protein expression. The MEK1/2 signaling cascade participates in H. pylori-mediated Egr-1 expression, but the p38 pathway does not. The data indicate that H. pylori induces Egr-1 expression in AGS cells in vitro and that the Egr-1 protein is readily detectable in biopsies from H. pylori-positive subjects. These observations suggest that H. pylori-associated Egr-1 expression may play a role, in part, in H. pylori-induced pathology.