title: Effects of KF19514, a phosphodiesterase 4 and 1 Inhibitor, on bronchial inflammation and remodeling in a murine model of chronic asthma.
abstract: BACKGROUND
  Phosphodiesterase 4 selective inhibitor may prevent airway inflammation and remodeling.
  
  
  OBJECTIVE
  The aim of this study was to investigate the effects of KF19514, a phosphodiesterase 4 and 1 dual inhibitor, on chronic airway inflammation and remodeling following chronic exposure to aerosolized antigen in mice.
  
  
  METHODS
  Ovalbumin (OVA) was administered intraperitoneally to BALB/c mice on days 0 and 14, and the mice were then exposed to aerosolized OVA daily for 4 weeks. Twenty-four hours following the final inhalation, bronchial responsiveness to acetylcholine was measured, and histologic examination and hydroxyproline content of the lung were evaluated.
  
  
  RESULTS
  Bronchial responsiveness to acetylcholine, number of inflammatory cells and eosinophils in the lamina propria, thickness of epithelial and subepithelial collagen layers, and hydroxyproline content of the lung increased following chronic exposure to OVA for 7 weeks. KF19514 significantly prevented all of these changes.
  
  
  CONCLUSIONS
  Phosphodiesterase 4 and 1 inhibitors such as KF19514 may help prevent bronchial hyperresponsiveness and chronic asthma-induced airway remodeling.
authors.affiliation: Department of Respiratory Medicine, National Hospital Organization Kanazawa Medical Center, Ishikawa, Japan. naika-k1@kinbyou.hosp.go.jp
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kita
authors.forename: Masaki
authors.initials: M
authors.lastname: Fujimura
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Myou
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Yuko
authors.initials: Y
authors.lastname: Waseda
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakao
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology / Q000517:prevention & control; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1 / Q000037:antagonists & inhibitors*; D005260:Female; D006909:Hydroxyproline / Q000378:metabolism; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000473:pathology; D009287:Naphthyridines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011657:Pulmonary Eosinophilia / Q000473:pathology / Q000517:prevention & control; D020545:Respiratory Mucosa / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D014132:Trachea / Q000473:pathology; D014611:Vaccination
chemical_list: C106878:KF 19514; D009287:Naphthyridines; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010047:Ovalbumin; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D000109:Acetylcholine; D006909:Hydroxyproline