title: Helicobacter pylori infection activates NF-kappa B in gastric epithelial cells.
abstract: OBJECTIVE
  Helicobacter pylori adheres to gastric epithelial cells and stimulates interleukin (IL)-8 production. This may be instrumental in neutrophil infiltration of the gastric epithelium that characterizes H. pylori gastritis. This study examined the molecular mechanisms leading to H. pylori-induced epithelial cell IL-8 production.
  
  
  METHODS
  Electrophoretic mobility shift analyses for NF-kappa B were performed on cell and nuclear extracts from H. pylori-infected AGS and Kato III human gastric epithelial cells.
  
  
  RESULTS
  H. pylori infection activated the transcription factor NF-kappa B and induced nuclear translocation of both NF-kappa B p50/p65 heterodimers and p50 homodimers. Nuclear translocation of NF-kappa B (30 minutes) was followed by increased IL-8 messenger RNA (1 hour) and protein levels (4 hours) consistent with NF-kappa B up-regulation of IL-8 gene transcription. Pretreatment of AGS cells with PDTC, which blocks NF-kappa B activation, inhibited H. pylori-induced increases in IL-8 production by 90%. Immunohistochemical studies using a monoclonal antibody that recognizes the I-kappa B binding region of p65 showed activated NF-kappa B in gastric epithelial cells of patients with H. pylori gastritis.
  
  
  CONCLUSIONS
  H. pylori infection activates NF-kappa B in gastric epithelial cells in vitro and in vivo. NF-kappa B is a transcriptional regulator of IL-8 production, and its activation after bacterial infection may be an important defense response in gastrointestinal epithelial cells.
authors.affiliation: Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: S
authors.initials: S
authors.lastname: Keates
authors.forename: Y S
authors.initials: YS
authors.lastname: Hitti
authors.forename: M
authors.initials: M
authors.lastname: Upton
authors.forename: C P
authors.initials: CP
authors.lastname: Kelly
mesh_terms: D001706:Biopsy; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D005753:Gastric Mucosa / Q000382:microbiology* / Q000473:pathology / Q000502:physiology*; D005805:Genes, MHC Class I; D016481:Helicobacter Infections / Q000473:pathology / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis*; D016328:NF-kappa B / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D007375:Interleukin-1; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D011994:Recombinant Proteins