Harris P R, Ernst P B, Kawabata S, Kiyono H, Graham M F, Smith P D
Department of Pediatrics, Oral Biology, University of Alabama at Birmingham, USA.
J Infect Dis. 1998 Nov;178(5):1516-20. doi: 10.1086/314426.
Helicobacter pylori urease is absorbed into the gastric mucosa at sites of inflammation, but whether the enzyme activates mucosal macrophages is not known. Because mucosal macrophages differ phenotypically and functionally from blood monocytes, whether recombinant H. pylori urease (rUrease) activated purified lamina propria macrophages in vitro was investigated. rUrease (1-10 microgram/mL) induced primary mucosal macrophages to produce interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha but not IL-8 proteins in a dose-dependent manner (P<.05 to P<.001). Quantitative reverse transcriptase-polymerase chain reaction using capillary electrophoresis laser-induced fluorescence showed that rUrease (0.1-10 microgram/mL) also induced dose-dependent expression of IL-1beta, IL-6, and TNF-alpha but not IL-8 mRNA (P<.05), suggesting that rUrease-induced production of certain cytokines is regulated at the level of gene transcription. These findings indicate that the ability of H. pylori urease to activate mucosal macrophages, resulting in production of proinflammatory cytokines, may be involved in the pathogenesis of H. pylori-associated mucosal inflammation.
幽门螺杆菌脲酶在炎症部位被吸收进入胃黏膜，但该酶是否激活黏膜巨噬细胞尚不清楚。由于黏膜巨噬细胞在表型和功能上与血液单核细胞不同，因此研究了重组幽门螺杆菌脲酶（rUrease）在体外是否能激活纯化的固有层巨噬细胞。rUrease（1 - 10微克/毫升）以剂量依赖方式诱导原代黏膜巨噬细胞产生白细胞介素（IL）-1β、IL-6和肿瘤坏死因子（TNF）-α，但不产生IL-8蛋白（P<0.05至P<0.001）。使用毛细管电泳激光诱导荧光的定量逆转录聚合酶链反应表明，rUrease（0.1 - 10微克/毫升）也以剂量依赖方式诱导IL-1β、IL-6和TNF-α的表达，但不诱导IL-8 mRNA的表达（P<0.05），这表明rUrease诱导的某些细胞因子的产生在基因转录水平受到调控。这些发现表明，幽门螺杆菌脲酶激活黏膜巨噬细胞从而导致促炎细胞因子产生的能力，可能参与了幽门螺杆菌相关黏膜炎症的发病机制。
