title: Interferon regulatory factor-2 regulates exocytosis mechanisms mediated by SNAREs in pancreatic acinar cells.
abstract: OBJECTIVE
  Pancreatic acinar cells are used to study regulated exocytosis. We investigated the role of interferon regulatory factor-2 (IRF2) in exocytosis in pancreatic acinar cells.
  
  
  METHODS
  Pancreas tissues from Irf2⁺/⁺, Irf2⁺/⁻), and Irf2⁻/⁻ mice were examined by microscopy, immunohistochemical, and immunoblot analyses; amylase secretion was quantified. We also compared salivary glands and pancreatic islets of Irf2⁻/⁻ mice with those of Irf2⁺/⁻ mice. To examine the effects of increased signaling by type I interferons, we studied pancreatic acini from Irf2⁻/⁻Ifnar1⁻/⁻ mice. The effect of IRF2 on amylase secretion was studied using an acinar cell line and a retroviral system. We studied expression of IRF2 in wild-type mice with cerulein-induced pancreatitis and changes in pancreatic tissue of Irf2⁻/⁻ mice, compared with those of Irf2⁺/⁻ mice.
  
  
  RESULTS
  Irf2⁻/⁻ pancreas was white and opaque; numerous and wide-spread zymogen granules were observed throughout the cytoplasm, along with lack of fusion between zymogen granules and the apical membrane, lack of secretagogue-stimulated amylase secretion, and low serum levels of amylase and elastase-1, indicating altered regulation of exocytosis. The expression pattern of soluble N-ethylmaleimide-sensitive factor attachment protein receptors changed significantly, specifically in pancreatic acini, and was not rescued by disruption of type I interferon signaling. Down-regulation of IRF2 decreased amylase secretion in an acinar cell line. In mice with pancreatitis, levels of IRF2 were reduced. Irf2⁻/⁻ acini were partially resistant to induction of pancreatitis.
  
  
  CONCLUSIONS
  IRF2 regulates exocytosis in pancreatic acinar cells; defects in this process might be involved in the early phases of acute pancreatitis.
authors.affiliation: Department of Gastroenterology, Akita University Graduate School of Medicine, Akita, Japan. hmashima1-tky@umin.ac.jp
authors.forename: Hirosato
authors.initials: H
authors.lastname: Mashima
authors.forename: Taku
authors.initials: T
authors.lastname: Sato
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Horie
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Itaru
authors.initials: I
authors.lastname: Kojima
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ohteki
authors.forename: Hirohide
authors.initials: H
authors.lastname: Ohnishi
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D002108:Ceruletide / Q000009:adverse effects; D004195:Disease Models, Animal; D005089:Exocytosis / Q000502:physiology*; D050836:Interferon Regulatory Factor-2 / Q000235:genetics / Q000502:physiology*; D007372:Interferons / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046790:Pancreas, Exocrine / Q000473:pathology* / Q000503:physiopathology*; D010195:Pancreatitis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D050600:SNARE Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D050836:Interferon Regulatory Factor-2; C494230:Irf2 protein, mouse; D050600:SNARE Proteins; D002108:Ceruletide; D007372:Interferons