Aihara M, Azuma A, Takizawa H, Tsuchimoto D, Funakoshi Y, Shindo Y, Ohmoto Y, Imagawa K, Kikuchi M, Mukaida N, Matsushima K
Microbiological Research Institute, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan.
Dig Dis Sci. 1998 Sep;43(9 Suppl):174S-180S.
Interleukin-8 (IL-8) may play an important role in Helicobacter pylori infection-associated chronic active gastritis and peptic ulcer disease in human. We have recently reported that a gastric cancer cell line, MKN45, produced a massive amount of IL-8 upon coculture with live H. pylori. Moreover, H. pylori induced the activation of NF-kappaB as well as AP-1, leading to IL-8 gene transcription. In this study, we evaluated the effect of rebamipide, an antigastritis and antiulcer agent, on H. pylori-induced IL-8 production. Rebamipide inhibited the production of IL-8 in several gastric cancer cell lines infected with H. pylori. In addition, rebamipide suppressed H. pylori-induced IL-8 gene expression at the transcriptional level as revealed by northern blotting analysis and luciferase activity in cells that were transfected with a luciferase expression vector linked with a 5'-flanking region of the IL-8 gene (bp -133 to +44). Furthermore, rebamipide significantly suppressed the NF-kappaB activation by H. pylori infection. These results suggest that rebamipide may protect against the mucosal inflammation associated with H. pylori infection through inhibition of a proinflammatory cytokine, IL-8.
白细胞介素-8（IL-8）可能在人类幽门螺杆菌感染相关的慢性活动性胃炎和消化性溃疡疾病中发挥重要作用。我们最近报道，胃癌细胞系MKN45与活的幽门螺杆菌共培养时会产生大量IL-8。此外，幽门螺杆菌诱导核因子κB（NF-κB）以及活化蛋白-1（AP-1）的激活，从而导致IL-8基因转录。在本研究中，我们评估了抗胃炎和抗溃疡药物瑞巴派特对幽门螺杆菌诱导的IL-8产生的影响。瑞巴派特抑制了几种感染幽门螺杆菌的胃癌细胞系中IL-8的产生。此外，如通过Northern印迹分析以及用与IL-8基因5'-侧翼区域（bp -133至+44）连接的荧光素酶表达载体转染的细胞中的荧光素酶活性所显示的，瑞巴派特在转录水平上抑制了幽门螺杆菌诱导的IL-8基因表达。此外，瑞巴派特显著抑制了幽门螺杆菌感染引起的NF-κB激活。这些结果表明，瑞巴派特可能通过抑制促炎细胞因子IL-8来预防与幽门螺杆菌感染相关的黏膜炎症。
