The molecular mechanism of te pathogenesis induced by Helicbacter phylori (TN2) and the clinical application

(1)H. pylori感染的分子机制。幽门螺杆菌介导的NF-κ B活化在胃上皮细胞系和单核细胞系中的表达。具有完整cag派的幽门螺杆菌通过涉及IkB激酶（IKK）、NF-κ B诱导激酶（NIK）、TRAF 2和TRAF 6的信号传导途径激活NF-κ B。在单核细胞系中，H. pylori介导的NF-kB激活涉及TLR 4，但不依赖于cag派。(2)H. pylori H. pylori通过激活ERK/MAPK级联反应激活人胃癌细胞SRE、c-fos和Cyclin D1的转录。(3)CagA蛋白对SRE的激活有报道称CagA蛋白可转位至上皮细胞并与细胞骨架重排有关。我们确定了CagA蛋白作为SRE激活剂的新作用。(4)cDNA微阵列分析H. pylori介导的基因表达改变我们比较了有和没有H. pylori共培养，通过使用内部cDNA微阵列。与cag派阳性菌株共培养后，2304个基因中有8个基因的mRNA表达显著上调。(5)本实验研究了cag派在H.幽门螺杆菌使用长期（62周）动物模型。用TN 2及其cagE或vacA等基因突变体攻击长爪沙鼠。cagE突变体感染沙鼠后无溃疡发生，仅引起轻度胃炎，派在H.此外，我们验证了一个3周的沙鼠模型，使用同基因突变体筛选H. pylori的促炎毒力决定因子。pylori in vivo.

(1) NF-kB activation by H. pyloriWe analyzed the molecular mechanism of H. pylori-mediated NF-kB activation in both a gastric epithelial cell line and in a monocytic cell line.In gastric cancer cells, H. pylori possessing intact cag PAI activates NF-kB through a signaling pathway involving IkB kinases (IKK's), NF-kB-inducing kinase (NIK), TRAF2, and TRAF6. In a monocytic cell line, H. pylori-mediated NF-kB activation involves TLR4 but is independent of cag PAI.(2) The activation of ERK/MARK cascade by H. pyloriH. pylori with intact cage PAI activated SRE, c-fos and Cyclin D1 transcription through the activation of ERK/MAPK cascade in human gastric cancer cells.(3) SRE activation by CagA proteinIt has been reported that CagA protein is translocated into epithelial cells and associated with cellular cytoskeletal rearrangements. We identified a new role of CagA protein as an activator of SRE.(4) cDNA microarray analysis of H. pylori-mediated alteration of gene expressionWe compared mRNA profiles in human gastric cancer cells with and without H. pylori cocultured by using an in-house cDNA microarray. Coculture with cag PAI positive strain significantly up-regulated mRNA expression in 8 of 2304 genes fested.(5) Mongolian gerbil infection modelWe examined the role of cag PAI in the gastric pathogenesis induced by H. pylori using a long-term (62 wk) animal model. Mongolian gerbils were challenged with TN2 and its isogenic mutants of cagE or vacA. No ulcer was found in the gerbils infected with the cagE mutant, and cagE mutants induced only mild gastritis cag PAI plays an essential role in the pathogenesis of gastric diseases related H. pylori infection.Furthermore, we validated a 3-week gerbil model using isogenic mutants for screening of proinflammatory virulence determinants of H. pylori in vivo.