Smoot D T, Wynn Z, Elliott T B, Allen C R, Mekasha G, Naab T, Ashktorab H
Department of Medicine, Howard University College of Medicine, Washington, DC, USA.
Am J Gastroenterol. 1999 Jun;94(6):1508-11. doi: 10.1111/j.1572-0241.1999.01134.x.
H. pylori infection of the gastric mucosa has been associated with an increase in gastric epithelial cell proliferation. However, in vitro adherence of H. pylori to gastric epithelial cells is associated with reduced cell proliferation. Reduction of epithelial cell proliferation may contribute to ulcer formation and delay ulcer healing. The following study was undertaken to elucidate the ability of cagA-positive and -negative strains to impede gastric epithelial cell proliferation.
A human gastric adenocarcinoma cell line (AGS) was overlaid with either cagA-positive or cagA-negative H. pylori strains suspended in cell culture medium. Proliferation of AGS cells was analyzed by performing direct cell counts and by measuring metabolism of a soluble tetrazolium compound (MTS), after exposure to H. pylori for 24 h.
When compared with control cells cultured in medium alone, AGS cell proliferation was reduced by 45.6% and 28.5% due to exposure to cagA-negative and cagA-positive strains, respectively. When bacterial-induced cytotoxicity was assessed by measuring release of lactose dehydrogenase (LDH) into the culture medium, cagA-positive strains were shown to induce significantly more cytotoxicity than cagA-negative strains.
These experiments demonstrate that H. pylori exposure to AGS cells significantly reduces cell proliferation. However, cagA-positive strains that induce more cell injury reduce cell proliferation to a lesser extent than cagA-negative strains. Persistent replication of gastric epithelial cells injured by exposure to cagA-positive strains may be partially responsible for the stronger association with gastric cancer in persons infected with cagA-positive H. pylori strains.
胃黏膜幽门螺杆菌感染与胃上皮细胞增殖增加有关。然而，幽门螺杆菌在体外与胃上皮细胞的黏附却与细胞增殖减少有关。上皮细胞增殖的减少可能导致溃疡形成并延迟溃疡愈合。开展以下研究以阐明细胞毒素相关基因A（cagA）阳性和阴性菌株阻碍胃上皮细胞增殖的能力。
将悬浮于细胞培养基中的cagA阳性或cagA阴性幽门螺杆菌菌株覆盖在人胃腺癌细胞系（AGS）上。在暴露于幽门螺杆菌24小时后，通过直接细胞计数和测量可溶性四氮唑化合物（MTS）的代谢来分析AGS细胞的增殖情况。
与仅在培养基中培养的对照细胞相比，暴露于cagA阴性和cagA阳性菌株后，AGS细胞增殖分别减少了45.6%和28.5%。通过测量培养基中乳酸脱氢酶（LDH）的释放来评估细菌诱导的细胞毒性时，结果显示cagA阳性菌株比cagA阴性菌株诱导的细胞毒性明显更大。
这些实验表明，幽门螺杆菌暴露于AGS细胞会显著降低细胞增殖。然而，诱导更多细胞损伤的cagA阳性菌株比cagA阴性菌株使细胞增殖减少的程度更小。暴露于cagA阳性菌株而受损的胃上皮细胞持续复制可能部分解释了感染cagA阳性幽门螺杆菌菌株的人患胃癌的关联性更强的原因。
