Helicobacter pylori infection:: pathogenesis
Helicobacter pylori infection:: pathogenesis
复制标题
DOI：
10.1097/00001574-200201000-00004
复制
发表时间：
2002-01-01
影响因子：
2.5
通讯作者：
Wang, TC
中科院分区：
文献类型：
--
作者：
Fox, JG;Wang, TC
幽门螺杆菌是引起胃溃疡和胃癌的主要原因。在没有根除的情况下，感染往往是终身的，免疫反应在清除细菌方面无效。许多研究小组已经研究了是否可以通过疫苗接种策略实现感染的免疫清除，但迄今为止，结果还没有定论。事实上，在大多数自然感染的情况下，宿主免疫反应导致胃粘膜内的慢性炎症，这实际上促进了萎缩和肿瘤的发展。在大多数情况下，根除有机体导致炎症消退，这在许多情况下可以导致萎缩和胃癌风险降低。这一发现表明，即使在晚期，癌症进展在很大程度上也取决于感染/免疫反应。许多实验室的工作提出了一个假设，即T细胞和Th 1免疫应答，主要受宿主遗传因素的控制，与H.幽门介导的萎缩和癌症的诱导。白细胞介素-1 β似乎是一种特别重要的细胞因子，其抑制酸分泌并增加血清胃泌素水平，这些因素与癌症诱导密切相关。H.幽门螺杆菌的细胞因子和趋化因子以及生长相关基因的表达是由MAPK和NF-κ B信号通路介导的。最近的研究表明，NF-κ B通过NF-κ B诱导激酶/p21激活激酶1途径激活。H. pylori还可以通过多种机制促进细胞凋亡，其中最重要的是上调Fas/FasL途径。最后，对H.基因组学和蛋白质组学在生物体中的应用拓宽并加深了幽门螺杆菌的发病机制。(C)2002年利平科特威廉姆斯&威尔金斯公司
Helicobacter pylori is known to be the cause of most gastric diseases, including both peptic ulcer disease and gastric cancer. In the absence of eradication, infection tends to be lifelong and the immune response ineffective in clearing the bacteria. A number of groups have investigated whether the immune clearance of infection can be achieved through a vaccination strategy, but to date, the results have been inconclusive. In fact, in most cases of natural infection, the host immune response leads to a chronic inflammation within the gastric mucosa that actually promotes the development of atrophy and neoplasia. In most cases, eradication of the organism leads to resolution of inflammation, which in many instances can result in reduction in atrophy and gastric cancer risk. This finding suggests that even at late stages, cancer progression is dependent, to a large extent, on infection/immune response. Work from a number of laboratories has led to the hypothesis that T-cells and the Th1 immune response, governed largely by host genetic factors, are strongly associated with the H. pylori mediated induction of atrophy and cancer. Interleukin-1 beta appears to be a particularly important cytokine that inhibits acid secretion and increases serum gastrin levels, factors strongly associated with cancer induction. The induction by H. pylori of cytokines and chemokines and growth-related genes is mediated by the MAPK and NF-kappaB signaling pathway. Recent studies have shown that NF-kappaB is activated through a NF-kappaB-inducing kinase/p21-activated kinase 1 pathway. H. pylori can also promote cellular apoptosis through a number of mechanisms, the most important of which is upregulation of the Fas/FasL pathway. Finally, understanding of H. pylori pathogenesis has been broadened and deepened by the application of genomics and proteomics to the organism. (C) 2002 Lippincott Williams & Wilkins, Inc.