Nottingham Digestive Diseases Centre Biomedical Research Unit, Queen's Medical Centre, University of Nottingham, Nottingham, United Kingdom.
J Infect Dis. 2010 Jul 15;202(2):261-9. doi: 10.1086/653587.
Infection with Helicobacter pylori possessing a newly described virulence factor--duodenal ulcer-promoting gene A (dupA)--has been associated with duodenal ulceration and increased gastric inflammation.
The dupA locus of 34 strains was sequenced. A panel of dupA mutants was generated and cocultured with human gastric epithelial cells and peripheral blood mononuclear cells; proinflammatory cytokine release was measured. IL8 expression was measured in human gastric biopsy specimens and related to the dupA and cagA status of infecting strains.
Most H. pylori strains had a dupA allele that was longer (1884 bp; dupA1) than previously described dupA alleles, although some had truncated versions (dupA2). Unlike the best-characterized H. pylori virulence determinant, the cag pathogenicity island (cag PaI), neither dupA type induced release of interleukin (IL)-8 from gastric epithelial cells. However, infections due to dupA-positive strains were associated with higher-level mucosal IL-8 messenger RNA expression in the human stomach than were infections due to dupA-negative strains. To explain this paradox, we found that dupA1 (but not dupA2 or the cag PaI) substantially increased H. pylori-induced IL-12p40 and IL-12p70 production from CD14(+) mononuclear cells. Other T helper 1-associated cytokines were also modestly induced.
We suggest that virulent H. pylori strains cause inflammation by stimulating epithelial cells through cag-encoded proteins and mononuclear inflammatory cells through dupA1 products.
感染具有新描述的毒力因子——十二指肠溃疡促进基因 A（dupA）的幽门螺杆菌与十二指肠溃疡和胃炎症增加有关。
对 34 株菌株的 dupA 基因座进行测序。生成了一组 dupA 突变体，并与人胃上皮细胞和外周血单核细胞共培养；测量促炎细胞因子的释放。测量人胃活检标本中的 IL8 表达，并与感染菌株的 dupA 和 cagA 状态相关。
大多数 H. pylori 菌株的 dupA 等位基因比以前描述的 dupA 等位基因更长（1884bp；dupA1），尽管有些是截断的版本（dupA2）。与最具特征的 H. pylori 毒力决定因素 cag 致病岛（cag PaI）不同，dupA 类型均未诱导胃上皮细胞释放白细胞介素（IL）-8。然而，dupA 阳性菌株引起的感染与 dupA 阴性菌株引起的感染相比，人胃黏膜 IL-8 信使 RNA 表达水平更高。为了解释这一矛盾，我们发现 dupA1（而非 dupA2 或 cag PaI）可显著增加 H. pylori 诱导的 CD14+单核细胞中 IL-12p40 和 IL-12p70 的产生。其他 Th1 相关细胞因子也略有诱导。
我们认为，毒力 H. pylori 菌株通过 cag 编码蛋白刺激上皮细胞，通过 dupA1 产物刺激单核炎性细胞，从而引起炎症。
