Peek R M, Thompson S A, Donahue J P, Tham K T, Atherton J C, Blaser M J, Miller G G
Department of Medicine, Vanderbilt University School of Medicine, Department of Veterans Affairs Medical Center, Nashville, TN 37232-2279, USA.
Proc Assoc Am Physicians. 1998 Nov-Dec;110(6):531-44.
Most persons infected with Helicobacter pylori strains that produce vacuolating cytotoxin and possess cytotoxin-associated gene A (cagA) genotype nonetheless remain asymptomatic, suggesting that additional genes are important in virulence. We hypothesized that adherence to gastric epithelium provides stimuli that induce expression of some virulence genes. Our aims were to identify expression of H. pylori genes induced by adherence and to determine if such genes were correlated with peptic ulceration, mucosal interleukin-8 (IL-8) levels, and gastric inflammation. RNA was isolated from an ulcer-derived strain and a gastritis-derived strain that were exposed or not exposed to gastric epithelial cells. These RNAs were used for random arbitrarily primed reverse transcription polymerase chain reaction to identify newly expressed transcripts unique to the ulcer-derived strain following adherence. Clinical isolates of H. pylori were characterized for presence of the newly identified gene, and mucosal IL-8 and inflammation were examined in gastric biopsies from the source patients. A novel H. pylori gene, iceA (induced by contact with epithelium), was identified. DNA sequences revealed two families, iceA1 and iceA2. iceA1 strains were significantly associated with peptic ulceration and increased mucosal concentrations of IL-8. Both iceA1 and iceA2 were expressed in vivo by respective H. pylori strains in gastric biopsies. Adherence to gastric epithelial cells in vitro stimulates the transcription of iceA1, an H. pylori gene that is highly correlated with pathological outcome.
大多数感染了产生空泡细胞毒素并具有细胞毒素相关基因A（cagA）基因型的幽门螺杆菌菌株的人仍然没有症状，这表明其他基因在致病性中也很重要。我们假设，对胃上皮的黏附提供了诱导某些毒力基因表达的刺激。我们的目的是确定黏附诱导的幽门螺杆菌基因的表达，并确定这些基因是否与消化性溃疡、黏膜白细胞介素-8（IL-8）水平和胃炎症相关。从暴露或未暴露于胃上皮细胞的溃疡源菌株和胃炎源菌株中分离RNA。这些RNA用于随机任意引物逆转录聚合酶链反应，以鉴定黏附后溃疡源菌株特有的新表达转录本。对幽门螺杆菌临床分离株进行新鉴定基因存在情况的特征分析，并对源患者的胃活检组织中的黏膜IL-8和炎症进行检查。鉴定出一种新的幽门螺杆菌基因iceA（由与上皮细胞接触诱导）。DNA序列揭示了两个家族，iceA1和iceA2。iceA1菌株与消化性溃疡和黏膜IL-8浓度升高显著相关。iceA1和iceA2在胃活检组织中各自的幽门螺杆菌菌株体内均有表达。体外对胃上皮细胞的黏附刺激了iceA1的转录，iceA1是一种与病理结果高度相关的幽门螺杆菌基因。
