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Inhibition of Helicobacter pylori ‐induced Nuclear Factor‐kappa B Activation and Interleukin‐8 Gene Expression by Ecabet Sodium in Gastric Epithelial Cells
Author(s) -
Kim Jung Mogg,
Kim Joo Sung,
Jung Hyun Chae,
Oh YuKyoung,
Kim Nayoung,
Song In Sung
Publication year - 2003
Publication title -
helicobacter
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.206
H-Index - 79
eISSN - 1523-5378
pISSN - 1083-4389
DOI - 10.1046/j.1523-5378.2003.00175.x
Subject(s) - helicobacter pylori , microbiology and biotechnology , chemistry , caga , gastric mucosa , western blot , biology , gene , stomach , biochemistry , genetics , virulence
Background. Helicobacter pylori stimulates nuclear factor‐kappa B (NF‐κB) activation and chemokine interleukin‐8 (IL‐8) expression in gastric epithelial cells. Ecabet sodium (ecabet), a locally acting antiulcer drug, is known to have anti‐ H. pylori activity. However, there is little understanding of how ecabet induces anti‐inflammatory activity in gastric epithelial cells infected with H. pylori . The aim of this study was to investigate the effects of ecabet on IL‐8 gene expression and NF‐κB activation in human gastric epithelial cells infected with H. pylori . Materials and Methods. After Hs746T, MKN‐45, or SNU‐5 gastric epithelial cell lines had been infected with cagA + cytotoxin + H. pylori in the presence of ecabet, IL‐8 mRNA expression was assessed by quantitative reverse transcription–polymerase chain reaction, and IL‐8 secretion was measured by enzyme‐linked immunosorbent assay. NF‐κB and inhibitory kappa B‐alpha (IκBα) signals were assayed by electrophoretic mobility shift assay and Western blot, respectively. The activation of NF‐κB and IL‐8 reporter genes was determined by luciferase assay. Results. Ecabet showed no antimicrobial activiy against Gram‐positive or ‐negative bacteria. However, ecabet inhibited transcription of the IL‐8 gene and secretion of IL‐8 by gastric epithelial cells infected with H. pylori at a concentration of 5 µg/ml. Moreover, ecabet inhibited the activation of NF‐κB and the degradation of IκBα in gastric epithelial cells in response to H. pylori infection. In addition, the NF‐κB signal inhibited by ecabet was comprised predominantly of heterodimers of p65/p50. Conclusions. Ecabet inhibited H. pylori ‐induced IL‐8 gene transcription and secretion by suppressing the NF‐κB signal. This inhibition might be one pathway by which ecabet exerts its anti‐inflammatory effect on H. pylori ‐induced gastric inflammation.