title: Molecular analysis of suppression of interleukin-8 production by rebamipide in Helicobacter pylori-stimulated gastric cancer cell lines.
abstract: 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.
authors.affiliation: Microbiological Research Institute, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Aihara
authors.forename: A
authors.initials: A
authors.lastname: Azuma
authors.forename: H
authors.initials: H
authors.lastname: Takizawa
authors.forename: D
authors.initials: D
authors.lastname: Tsuchimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Funakoshi
authors.forename: Y
authors.initials: Y
authors.lastname: Shindo
authors.forename: Y
authors.initials: Y
authors.lastname: Ohmoto
authors.forename: K
authors.initials: K
authors.lastname: Imagawa
authors.forename: M
authors.initials: M
authors.lastname: Kikuchi
authors.forename: N
authors.initials: N
authors.lastname: Mukaida
authors.forename: K
authors.initials: K
authors.lastname: Matsushima
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016480:Helicobacter pylori; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D015363:Quinolones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000382:microbiology; D014407:Tumor Cells, Cultured
chemical_list: D000897:Anti-Ulcer Agents; D017931:DNA Primers; D016209:Interleukin-8; D015363:Quinolones; D012333:RNA, Messenger; C052785:rebamipide; D000409:Alanine