Inhibition of lipid peroxidation, NF-kappaB activation and IL-8 production by rebamipide in Helicobacter pylori-stimulated gastric epithelial cells.
The present study aimed to investigate whether rebamipide, a novel antiulcer agent that has an oxygen radical scavenging activity, would inhibit lipid peroxidation, NF-kappaB activation, and IL-8 production by H. pylori. Human gastric epithelial cells (AGS and KATO III), treated with rebamipide or not were incubated in the absence or the presence of H. pylori. As a result, H. pylori significantly stimulated IL-8 production, which was similar to time course stimulation of lipid peroxidation. Other cytokines (IL-1alpha, IL-1beta, IL-6, TNF-alpha) were not stimulated by H. pylori. Treatment with H. pylori resulted in the activation of two species of NF-kappaB dimers (a p50/p65 heterodimer and a p50 homodimer). Rebamipide significantly inhibited lipid peroxidation as an indicative of oxidative damage, NF-kappaB complex formation, and IL-8 production by H. pylori. In conclusion, rebamipide may attenuate H. pylori-induced gastric inflammation by inhibiting lipid peroxidation and oxidant-mediated activation of NF-kappaB and thereby decreasing IL-8 production.
Kim
H
H
Department of Pharmacology and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
Seo
J Y
JY
Kim
K H
KH
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism*; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D015227:Lipid Peroxidation / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism*; D015363:Quinolones / Q000494:pharmacology*
D000897:Anti-Ulcer Agents; D016207:Cytokines; D016166:Free Radical Scavengers; D016209:Interleukin-8; D016328:NF-kappa B; D015363:Quinolones; C052785:rebamipide; D000409:Alanine