title: Inhibition of Helicobacter pylori-induced nuclear factor-kappa B activation and interleukin-8 gene expression by ecabet sodium in gastric epithelial cells.
abstract: BACKGROUND
  Helicobacter pylori stimulates nuclear factor-kappa B (NF-kappa B) 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-kappa B activation in human gastric epithelial cells infected with H. pylori.
  
  
  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-kappa B and inhibitory kappa B-alpha (I kappa B alpha) signals were assayed by electrophoretic mobility shift assay and Western blot, respectively. The activation of NF-kappa B 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 micro g/ml. Moreover, ecabet inhibited the activation of NF- kappa B and the degradation of I kappa B alpha in gastric epithelial cells in response to H. pylori infection. In addition, the NF-kappa B 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-kappa B signal. This inhibition might be one pathway by which ecabet exerts its anti-inflammatory effect on H. pylori-induced gastric inflammation.
authors.affiliation: Department of Microbiology and Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Jung Mogg
authors.initials: JM
authors.lastname: Kim
authors.forename: Joo Sung
authors.initials: JS
authors.lastname: Kim
authors.forename: Hyun Chae
authors.initials: HC
authors.lastname: Jung
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.forename: In Sung
authors.initials: IS
authors.lastname: Song
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D016480:Helicobacter pylori / Q000187:drug effects / Q000472:pathogenicity*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D045784:Abietanes; D020672:I-kappa B Proteins; D016209:Interleukin-8; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha; C061681:ecabet; D008156:Luciferases