title: Upregulation of mucosal soluble fas ligand and interferon-gamma may be involved in ulcerogenesis in patients with Helicobacter pylori-positive gastric ulcer.
abstract: BACKGROUND
  Excessive upregulation of gastric epithelial cell apoptosis is speculated to be associated with ulcerogenesis in Helicobacter pylori-positive peptic ulcer disease. H. pylori may have an ulcerogenic effect through induction of gastric epithelial cell apoptosis mediated by infiltrating T cells and their soluble products.
  
  
  METHODS
  The contents of soluble Fas ligand (sFasL) and interferon-gamma (IFN-gamma) in organ cultures and the degree of apoptosis and the expression of apoptosis-related proteins in the gastric epithelium were examined using the mucosal tissues obtained from the antrum and the ulcer site in patients with H. pylori-positive gastric ulcer (GU). The molecular mechanisms of gastric epithelial cell apoptosis induced by sFasL and IFN-gamma were analyzed using epithelial cell lines, MKN 45 and KATO III.
  
  
  RESULTS
  The mucosal tissues of the ulcer site had substantially higher contents of sFasL and IFN-gamma in organ cultures regardless of its healing stage in association with increased numbers of apoptotic cells and enhanced expression of proapoptotic proteins Bak and Bax in the surface foveolar epithelium as compared with the antral tissues in patients with H. pylori-positive GU. The addition of sFasL caused increases in cytotoxic cell death and caspase-3 activation in MKN 45 and KATO III cells in which IFN-gamma treated cells had more prominent effects than untreated cells. The expression of Bak in MKN 45 cells increased when they were treated with IFN-gamma.
  
  
  CONCLUSIONS
  Upregulation of mucosal sFasL and IFN-gamma may be involved in ulcerogenesis in patients with H. pylori-positive GU through induction of gastric epithelial cell apoptosis.
authors.affiliation: First Dept of Internal Medicine, Nagoya University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shimada
authors.forename: K
authors.initials: K
authors.lastname: Ina
authors.forename: K
authors.initials: K
authors.lastname: Kyokane
authors.forename: A
authors.initials: A
authors.lastname: Imada
authors.forename: H
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Nishio
authors.forename: M
authors.initials: M
authors.lastname: Hayakawa
authors.forename: Y
authors.initials: Y
authors.lastname: Iinuma
authors.forename: M
authors.initials: M
authors.lastname: Ohta
authors.forename: T
authors.initials: T
authors.lastname: Ando
authors.forename: K
authors.initials: K
authors.lastname: Kusugami
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D053222:Fas Ligand Protein; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology / Q000503:physiopathology; D019254:Genes, bcl-2 / Q000235:genetics / Q000276:immunology; D016481:Helicobacter Infections / Q000276:immunology* / Q000503:physiopathology; D016480:Helicobacter pylori; D006801:Humans; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2; D013276:Stomach Ulcer / Q000276:immunology* / Q000382:microbiology* / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein
chemical_list: C494772:BAK1 protein, human; C494826:BAX protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D007371:Interferon-gamma; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases