Ogura K, Takahashi M, Maeda S, Ikenoue T, Kanai F, Yoshida H, Shiratori Y, Mori K, Mafune K I, Omata M
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Dig Dis Sci. 1998 Dec;43(12):2738-43. doi: 10.1023/a:1026671815512.
Interleukin-8 (IL-8) production by the gastric mucosa is increased in Helicobacter pylori infection. Previous studies indicated that H. pylori induces IL-8 synthesis in cancer cell lines, and the ability of H. pylori to stimulate IL-8 production is supposed to be associated with cagA and other cag pathogenicity island genes, including picB gene. In the present study, we investigated the induction of IL-8 in primary cultures of normal human gastric epithelial cells to elucidate the IL-8 induction by wild type strains and by the picB knockout strain. Human gastric epithelial cells were obtained from surgically resected specimens from four patients. Three H. pylori strains (TN2F4; type 1 clinical isolate, TN2F4m1; isogenic picB mutant of TN2F4, Tx30a; type 2 strain) were cocultured with the normal gastric epithelial cells or the transformed MKN-28. IL-8 levels in culture medium were determined by enzyme immunoassay. Human gastric epithelial cells produced IL-8 at a 10-50 times higher level than MKN-28 did when cocultured with TN2F4. The mutant TN2F4m1 induced IL-8 at significantly lower levels than the parent strain. Cells from four patients behaved similarly on IL-8 production. The results of the present study demonstrated the induction of IL-8 in normal gastric epithelial cells, suggesting that picB gene product may play an essential role in vivo.
幽门螺杆菌感染时,胃黏膜白细胞介素-8(IL-8)的产生会增加。先前的研究表明,幽门螺杆菌可诱导癌细胞系中IL-8的合成,并且幽门螺杆菌刺激IL-8产生的能力被认为与cagA及其他cag致病岛基因(包括picB基因)有关。在本研究中,我们调查了正常人胃上皮细胞原代培养物中IL-8的诱导情况,以阐明野生型菌株和picB基因敲除菌株对IL-8的诱导作用。从4例患者手术切除的标本中获取人胃上皮细胞。将3株幽门螺杆菌菌株(TN2F4;1型临床分离株,TN2F4m1;TN2F4的同基因picB突变体,Tx30a;2型菌株)与正常胃上皮细胞或转化的MKN-28共培养。通过酶免疫测定法测定培养基中的IL-8水平。当与TN2F4共培养时,人胃上皮细胞产生IL-8的水平比MKN-28高10至50倍。突变体TN2F4m1诱导产生IL-8的水平明显低于亲本菌株。4例患者的细胞在IL-8产生方面表现相似。本研究结果证明了正常胃上皮细胞中IL-8的诱导,提示picB基因产物可能在体内发挥重要作用。