Adherence to gastric epithelial cells induces expression of a Helicobacter pylori gene, iceA, that is associated with clinical outcome.

Adherence to gastric epithelial cells induces expression of a Helicobacter pylori gene, iceA, that is associated with clinical outcome.
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DOI:
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发表时间:
1998
期刊:
Proceedings of the Association of American Physicians
影响因子:
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通讯作者:
R. Peek;S. Thompson;J. Donahue;K. Tham;J. Atherton;M. Blaser;Geraldine G. Miller
R. Peek;S. Thompson;J. Donahue;K. Tham;J. Atherton;M. Blaser;Geraldine G. Miller
中科院分区:
其他
文献类型:
--
作者:
R. Peek;S. Thompson;J. Donahue;K. Tham;J. Atherton;M. Blaser;Geraldine G. Miller

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大多数人感染幽门螺杆菌菌株,产生空泡细胞毒素,并拥有细胞毒素相关基因A(cagA)基因型,但仍然没有症状,这表明其他基因是重要的毒力。我们假设,粘附到胃上皮细胞提供刺激,诱导某些毒力基因的表达。我们的目的是鉴定H. pylori基因,并确定这些基因是否与消化性溃疡,粘膜白细胞介素-8(IL-8)水平和胃炎症相关。从暴露于或不暴露于胃上皮细胞的溃疡衍生菌株和胃炎衍生菌株中分离RNA。这些RNA用于随机任意引发的逆转录聚合酶链反应,以鉴定粘附后溃疡衍生菌株特有的新表达转录本。临床分离的H. pylori的特征在于新鉴定的基因的存在,并且在来源患者的胃活组织检查中检查粘膜IL-8和炎症。小说H. pylori基因,iceA(通过与上皮接触诱导)。DNA序列显示了两个家族,iceA 1和iceA 2。iceA 1菌株与消化性溃疡和IL-8粘膜浓度增加显著相关。iceA 1和iceA 2均在H.幽门螺杆菌菌株。体外粘附胃上皮细胞可刺激H. pylori基因与病理结果高度相关。
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.