Suppression of Helicobacter pylori-induced interleukin-8 production in gastric cancer cell lines by an anti-ulcer drug, geranylgeranylacetone.
BACKGROUND
Geranylgeranylacetone (GGA) is an antigastritis and anti-ulcer agent, with as yet an unknown mechanism of action. In this study, we investigated the effect of GGA on Helicobacter pylori-induced interleukin (IL)-8 production and IL-8 mRNA expression in KATOIII cells, an established gastric cell line.


METHODS
Interleukin-8 production in H. pylori-infected KATOIII cells was measured by using enzyme-linked immunoassay. The cytotoxicity of H. pylori on KATOIII cells was measured by a 51Cr release assay. The effect of GGA on H. pylori-induced IL-8 mRNA expression was measured by using northern blotting.


RESULTS
Interleukin-8 production increased with time and H. pylori dose; the most significant increase was seen within 6-24 h of coculture with H. pylori. A dose of 0.1 mmol GGA suppressed IL-8 production (P = 0.0077) and inhibited H. pylori-induced IL-8 mRNA expression (P = 0.0019). Furthermore, H. pylori-induced gastric mucosal cell injury associated with IL-8 and neutrophil activation was enhanced by NH3, and this enhancement was suppressed by GGA (P = 0.0043).


CONCLUSIONS
Helicobacter pylori-infected gastric mucosal cells produce IL-8, which can promote neutrophil activation, thus contributing to mucosal tissue injury associated with H. pylori infection. Agents like GGA, which can suppress IL-8 production may have a protective role in the treatment of mucosal tissue damage seen in H. pylori infection.
Yoshimura
Naoki
N
The Second Department of Internal Medicine, Chiba University Hospital, Graduate School of Medicine, Chiba University, Japan. noaki@intmed02.m.chiba-u.ac.jp
Suzuki
Yasuo
Y
Saito
Yasushi
Y
D000704:Analysis of Variance; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D004224:Diterpenes / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D018375:Neutrophil Activation; D012333:RNA, Messenger / Q000096:biosynthesis; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000382:microbiology; D014407:Tumor Cells, Cultured
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D016209:Interleukin-8; D012333:RNA, Messenger; C031049:geranylgeranylacetone