Wagner S, Beil W, Westermann J, Logan R P, Bock C T, Trautwein C, Bleck J S, Manns M P
Department of Gastroenterology, Medizinische Hochschule Hannover, Germany. Wagner.Siegfried@MH-Hannover
Gastroenterology. 1997 Dec;113(6):1836-47. doi: 10.1016/s0016-5085(97)70003-9.
BACKGROUND & AIMS: Helicobacter pylori may affect the normal balance between gastric epithelial cell proliferation and epithelial cell death, thus interfering with the maintenance of gastric mucosal integrity. The aim of this study was to investigate the effect of H. pylori on cell growth, DNA synthesis, induction of apoptosis, and viability of human gastric epithelial cells in vitro.
H. pylori was incubated with a differentiated human gastric cancer cell line for up to 72 hours, and the effects on cell numbers (cell counts and WST-1 assay), DNA synthesis (5-bromo-2'-deoxyuridine assay and [3H]thymidine incorporation), and DNA fragmentation (DNA fluorochrome staining, transmission electron microscopy, and histone enzyme-linked immunosorbent assay) were assessed.
Incubation of gastric epithelial cells with H. pylori led to a time- and concentration-dependent reduction of epithelial cell growth and a concomitant induction of DNA fragmentation. At high bacteria-cell ratios (> 100), inhibition of cell growth was associated with a reduction in DNA synthesis. Treatment of gastric cells with tumor necrosis factor alpha, a receptor-activating CD95/APO-1/Fas antibody, and interferon gamma markedly potentiated H. pylori-induced DNA fragmentation.
H. pylori affects gastric epithelial cell growth by direct induction of apoptosis and inhibition of DNA synthesis and indirectly by sensitization of epithelial cells for apoptosis induced by proinflammatory stimuli.
幽门螺杆菌可能影响胃上皮细胞增殖与上皮细胞死亡之间的正常平衡，从而干扰胃黏膜完整性的维持。本研究旨在探讨幽门螺杆菌对体外培养的人胃上皮细胞生长、DNA合成、凋亡诱导及细胞活力的影响。
将幽门螺杆菌与人胃癌分化细胞系共孵育长达72小时，并评估其对细胞数量（细胞计数和WST-1检测）、DNA合成（5-溴-2'-脱氧尿苷检测和[3H]胸腺嘧啶核苷掺入）及DNA片段化（DNA荧光染色、透射电子显微镜检查和组蛋白酶联免疫吸附测定）的影响。
幽门螺杆菌与人胃上皮细胞共孵育导致上皮细胞生长呈时间和浓度依赖性降低，并伴随DNA片段化的诱导。在高细菌-细胞比例（>100）时，细胞生长抑制与DNA合成减少相关。用肿瘤坏死因子α、受体激活型CD95/APO-1/Fas抗体和干扰素γ处理胃细胞可显著增强幽门螺杆菌诱导的DNA片段化。
幽门螺杆菌通过直接诱导凋亡和抑制DNA合成以及间接使上皮细胞对促炎刺激诱导的凋亡敏感来影响胃上皮细胞生长。
