Cutting edge:: Urease release by Helicobacter pylori stimulates macrophage inducible nitric oxide synthase
Cutting edge:: Urease release by Helicobacter pylori stimulates macrophage inducible nitric oxide synthase
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DOI：
10.4049/jimmunol.168.12.6002
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发表时间：
2002-06-15
影响因子：
4.4
通讯作者：
Wilson, KT
中科院分区：
文献类型：
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作者：
Gobert, AP;Mersey, BD;Wilson, KT
诱导型NO合成酶（iNOS）的表达和NO的产生在体内和体外均因幽门螺杆菌感染而上调。我们通过将巨噬细胞与缺乏VacA、CagA、picB产物或脲酶（尿素（-））的野生型或突变型菌株共培养，确定了幽门螺杆菌释放的主要致病性蛋白是否激活iNOS。当使用过滤器从巨噬细胞中分离幽门螺杆菌时，与野生型和其他突变体相比，尿素（-）菌株受刺激的iNOS mRNA、蛋白质和NO2-产量选择性显著降低。同样，除了尿素-外，所有菌株的幽门螺杆菌蛋白水提取物均增加了巨噬细胞NO2的生成。重组脲酶刺激巨噬细胞iNOS表达和NO2-生成显著增加。综上所述，这些发现表明幽门螺杆菌必需生存因子脲酶在no依赖性粘膜损伤和癌变中发挥了新的作用。
Inducible NO synthase (iNOS) expression and production of NO are both up-regulated with Helicobacter pylori infection in vivo and in vitro. We determined whether major pathogenicity proteins released by H. pylori activate iNOS by coculturing macrophages with wild-type or mutant strains deficient in VacA, CagA, picB product, or urease (ureA(-)). When filters were used to separate H. pylori from macrophages, there was a selective and significant decrease in stimulated iNOS mRNA, protein, and NO2- production with the ureA(-) strain compared with wild-type and other mutants. Similarly, macrophage NO2- generation was increased by H. pylori protein water extracts of all strains except ureA-. Recombinant urease stimulated significant increases in macrophage iNOS expression and NO2- production. Taken together, these findings indicate a new role for the essential H. pylori survival factor, urease, implicating it in NO-dependent mucosal damage and carcinogenesis.