Regulation of gastric epithelial cell growth by Helicobacter pylori: Evidence for a major role of apoptosis
Regulation of gastric epithelial cell growth by Helicobacter pylori: Evidence for a major role of apoptosis
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DOI：
10.1016/s0016-5085(97)70003-9
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发表时间：
1997-12-01
期刊：
影响因子：
29.4
通讯作者：
Manns, MP
中科院分区：
文献类型：
--
作者：
Wagner, S;Beil, W;Manns, MP
背景与目的：幽门螺杆菌可能影响胃上皮细胞增殖与死亡之间的正常平衡，从而干扰胃粘膜完整性的维持。本研究的目的是探讨幽门螺杆菌对体外培养的人胃上皮细胞生长、DNA合成、细胞凋亡和存活率的影响。方法：将幽门螺杆菌与人胃癌细胞株共孵育72h，观察其对细胞数量(细胞计数和WST-1法)、DNA合成(5-溴-2‘-脱氧尿嘧啶核苷和[H-3]胸腺嘧啶核苷掺入法)和DNA断裂(DNA荧光染色、透射电子显微镜和组蛋白酶联免疫吸附试验)的影响。结果：幽门螺杆菌与胃上皮细胞孵育后，胃上皮细胞生长呈时间和浓度依赖性下降，并伴随DNA片段化。在高细菌-细胞比率(>；100)下，细胞生长抑制与DNA合成减少有关。用肿瘤坏死因子α(一种受体激活的CD95/APO-1/Fas抗体)和干扰素伽马处理胃细胞，可显著增强幽门螺杆菌诱导的DNA断裂。结论：幽门螺杆菌通过直接诱导胃上皮细胞凋亡和抑制DNA合成而影响胃上皮细胞的生长，间接地通过致炎刺激诱导上皮细胞的凋亡而影响胃上皮细胞的生长。
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. Methods: 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 [H-3]thymidine incorporation), and DNA fragmentation (DNA fluorochrome staining, transmission electron microscopy, and histone enzyme-linked immunosorbent assay) were assessed. Results: 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. Conclusions: 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.