Pai R, Wyle F A, Cover T L, Itani R M, Domek M J, Tarnawski A S
Department of Veterans Affairs Medical Center, Long Beach, CA 90822, USA.
Am J Pathol. 1998 Jun;152(6):1617-24.
The mechanisms by which Helicobacter pylori infection leads to gastroduodenal ulceration remain poorly understood. Previous studies have shown that H. pylori vacuolating cytotoxin (VacA) inhibits proliferation of gastric epithelial cells, which suggests that H pylori may interfere with gastric mucosal repair mechanisms. In this study, we investigated the effects of H. pylori broth culture supernatants on epidermal growth factor (EGF)-mediated signal transduction pathways in a gastric carcinoma cell line (KATO III). Exposure of these cells to EGF resulted in increased expression and phosphorylation of the EGF receptor (EGF-R), increased ERK2 activity and phosphorylation, and increased c-fos protein levels. Preincubation of cells with broth culture supernatant from VacA (+) H. pylori strain 60190 inhibited the capacity of EGF to induce each of these effects. In contrast, preincubation of cells with broth culture supernatant from an isogenic VacA-mutant strain (H. pylori 60190-v1) failed to inhibit the effects of EGF. These results suggest that the H. pylori vacuolating cytotoxin interferes with EGF-activated signal transduction pathways, which are known to be essential for cell proliferation and ulcer healing.
幽门螺杆菌感染导致胃十二指肠溃疡的机制仍未完全明确。以往研究表明，幽门螺杆菌空泡毒素（VacA）可抑制胃上皮细胞增殖，这提示幽门螺杆菌可能干扰胃黏膜修复机制。在本研究中，我们调查了幽门螺杆菌肉汤培养上清液对胃癌细胞系（KATO III）中表皮生长因子（EGF）介导的信号转导通路的影响。将这些细胞暴露于EGF会导致EGF受体（EGF-R）的表达和磷酸化增加、ERK2活性和磷酸化增加以及c-fos蛋白水平增加。用VacA（+）幽门螺杆菌菌株60190的肉汤培养上清液对细胞进行预孵育可抑制EGF诱导这些效应的能力。相比之下，用同基因VacA突变菌株（幽门螺杆菌60190-v1）的肉汤培养上清液对细胞进行预孵育未能抑制EGF的效应。这些结果表明，幽门螺杆菌空泡毒素干扰了EGF激活的信号转导通路，而该通路已知对细胞增殖和溃疡愈合至关重要。
