title: Lafutidine inhibits Helicobacter pylori-induced interleukin-8 production in human gastric epithelial cells.
abstract: OBJECTIVE
  Attachment of Helicobacter pylori to gastric epithelial cells leads to the production of chemokines, such as interleukin-8 (IL-8), which in turn activate and recruit neutrophils to the site of infection. Lafutidine [(+/-)-2-(furfurylsulfinyl)-N-(4-(4-(piperidinomethyl)-2-pyridyl)oxy-(Z)-2-butenyl)acetamide] is a new type of antiulcer drug that possesses an antisecretory action as well as gastroprotective activity, independent of its antisecretory action. In the present study, we examined the effects of lafutidine on H. pylori-induced IL-8 release and H. pylori adhesion to MKN45 cells.
  
  
  METHODS
  MKN45 cells were stimulated with H. pylori, tumor necrosis factor (TNF)-alpha, or IL-1beta, then IL-6 and IL-8 levels in the culture supernatants were determined with a specific enzyme-linked immunosorbent assay kit.
  
  
  RESULTS
  Lafutidine significantly inhibited both the release of IL-8 induced by H. pylori and the adhesion of H. pylori to cells in a dose-dependent manner. These properties of lafutidine are unrelated to the blockade of histamine H(2)-receptors, because the same effects have not been observed with other H(2)-receptor antagonists, such as cimetidine and famotidine. Lafutidine also significantly inhibited H. pylori-induced IL-6 release. Both TNF-alpha and IL-1beta-induced IL-8 releases, conversely, were little affected by lafutidine up to a concentration of 10(-5) M.
  
  
  CONCLUSIONS
  These results suggest that lafutidine inhibits IL-8 release by inhibiting H. pylori adherence to gastric epithelial cells, indicating a novel mechanism by which lafutidine protects against the mucosal inflammation associated with H. pylori infection.
authors.affiliation: Pharmacobioregulation Research Laboratory, Taiho Pharmaceutical Co. Ltd, 1-27 Misugidai, Hanno-shi, Saitama 357-8527, Japan. y-nozawa@taiho.co.jp
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nozawa
authors.forename: Katsushi
authors.initials: K
authors.lastname: Nishihara
authors.forename: Yushiro
authors.initials: Y
authors.lastname: Akizawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Orimoto
authors.forename: Motoko
authors.initials: M
authors.lastname: Nakano
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Uji
authors.forename: Hirofusa
authors.initials: H
authors.lastname: Ajioka
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Kanda
authors.forename: Naosuke
authors.initials: N
authors.lastname: Matsuura
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kiniwa
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis*; D010880:Piperidines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000081:Acetamides; D000897:Anti-Ulcer Agents; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D010880:Piperidines; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; C076948:lafutidine