Molecular analysis of suppression of interleukin-8 production by rebamipide in Helicobacter pylori-stimulated gastric cancer cell lines.
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.
Aihara
M
M
Microbiological Research Institute, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan.
Azuma
A
A
Takizawa
H
H
Tsuchimoto
D
D
Funakoshi
Y
Y
Shindo
Y
Y
Ohmoto
Y
Y
Imagawa
K
K
Kikuchi
M
M
Mukaida
N
N
Matsushima
K
K
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
D000897:Anti-Ulcer Agents; D017931:DNA Primers; D016209:Interleukin-8; D015363:Quinolones; D012333:RNA, Messenger; C052785:rebamipide; D000409:Alanine