A secreted/shed product of Helicobacter pylori activates transcription factor nuclear factor-kappa B.
A secreted/shed product of Helicobacter pylori activates transcription factor nuclear factor-kappa B.
复制标题
幽门螺杆菌的分泌/脱落产物可激活转录因子核因子-κ B。
作者：
A. Münzenmaier;C. Lange;Erik Glocker;A. Covacci;A. Moran;Stefan Bereswill;P. Baeuerle;M. Kist;Heike L. Pahl
幽门螺杆菌是慢性胃炎、十二指肠溃疡和胃腺癌发展的病因。胃上皮细胞暴露于幽门螺杆菌会诱导细胞因子 IL-8 的分泌，其在幽门螺杆菌感染的免疫发病机制中发挥关键作用。分离的螺杆菌菌株的毒力和诱导细胞因子产生的能力不同。高毒力与 IL-8 产生增强相关。然而，螺杆菌致病性差异的分子机制仍知之甚少。在这里，我们表明幽门螺杆菌介导的 IL-8 分泌需要激活胃上皮细胞系中的转录因子核因子 -kappaB (NF-kappaB)。一些不能诱导 IL-8 分泌的幽门螺杆菌菌株不会激活 NF-κB，而所有 IL-8 诱导菌株都会激活转录因子。此外，抗氧化剂姜黄素可抑制 NF-kappaB 激活，也完全抑制幽门螺杆菌诱导的 IL-8。 NF-kappaB 激活不是由 LPS 介导的，因为纯化的幽门螺杆菌 LPS 对胃上皮细胞没有影响。相比之下，IL-8 分泌和 NF-κB 激活都需要幽门螺杆菌分泌产物，而 picB/cagE（一种最近鉴定的假定转运蛋白）突变的菌株不会分泌该产物。
Helicobacter pylori is an etiologic agent in the development of chronic gastritis, duodenal ulceration, and gastric adenocarcinoma. Exposure of gastric epithelial cells to H. pylori induces secretion of the cytokine IL-8, which plays a pivotal role in the immunopathogenesis of H. pylori infections. Isolated Helicobacter strains differ in their virulence and in their ability to induce cytokine production. High degrees of virulence correlate with enhanced IL-8 production. However, the molecular mechanism of this variance in Helicobacter pathogenicity remains poorly understood. Here we show that H. pylori-mediated IL-8 secretion requires activation of the transcription factor nuclear factor-kappaB (NF-kappaB) in a gastric epithelial cell line. Several H. pylori strains which fail to induce IL-8 secretion do not activate NF-kappaB, while all IL-8-inducing strains activate the transcription factor. Moreover, the antioxidant curcumin, which inhibits NF-kappaB activation, also completely suppresses IL-8 induction by H. pylori. NF-kappaB activation is not mediated by LPSs, since purified H. pylori LPS had no effect on gastric epithelial cells. In contrast, both IL-8 secretion and NF-kappaB activation require a secreted H. pylori product, which is not secreted by strains mutated in picB/cagE, a recently identified putative transport protein.