Regulation of Helicobacter pylori cagA expression in response to salt
Regulation of Helicobacter pylori cagA expression in response to salt
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DOI：
10.1158/0008-5472.can-06-4746
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发表时间：
2007-05-15
期刊：
影响因子：
11.2
通讯作者：
Cover, Timothy L.
中科院分区：
文献类型：
--
作者：
Loh, John T.;Torres, Victor J.;Cover, Timothy L.
幽门螺杆菌感染和高盐饮食摄入是胃腺癌发生的危险因素。在这项研究中，我们测试了假设，高盐浓度可能会改变基因表达的H。幽门。转录谱实验表明，多个H。pylori基因，包括cagA，响应于细菌培养基中存在的氯化钠浓度而受到调节。通过使用转录报告菌株和免疫印迹证实了cagA在高盐条件下的表达增加。H.幽门螺杆菌CagA通过IV型分泌途径易位到胃上皮细胞中，并且在进入靶细胞时，CagA经历酪氨酸磷酸化并引起多种细胞改变。胃上皮细胞与H. pylori在高盐条件下生长，与细胞与H. pylori共培养相比，导致上皮细胞酪氨酸磷酸化CagA增加，白细胞介素8分泌增加。pylori在低盐条件下生长。上调H. pylori cagA在高盐浓度下的表达可能是促进胃腺癌发生的一个因素。
Helicobacter pylori infection and a high dietary salt intake are risk factors for the development of gastric adenocarcinoma. In this study, we tested the hypothesis that high salt concentrations might alter gene expression in H. pylori. Transcriptional profiling experiments indicated that the expression of multiple H. pylori genes, including cagA, was regulated in response to the concentrations of sodium chloride present in the bacterial culture medium. Increased expression of cagA in response to high salt conditions was confirmed by the use of transcriptional reporter strains and by immunoblotting. H. pylori CagA is translocated into gastric epithelial cells via a type IV secretion pathway, and on entry into target cells, CagA undergoes tyrosine phosphorylation and causes multiple cellular alterations. Coculture of gastric epithelial cells with H. pylori grown under high salt conditions resulted in increased tyrosine-phosphorylated CagA and increased secretion of interleukin-8 by the epithelial cells compared with coculture of the cells with H. pylori grown under low salt conditions. Up-regulation of H. pylori cagA expression in response to high salt concentrations may be a factor that contributes to the development of gastric adenocarcinoma.