Effects of KF19514, a phosphodiesterase 4 and 1 Inhibitor, on bronchial inflammation and remodeling in a murine model of chronic asthma.
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.
Kita
Toshiyuki
T
Department of Respiratory Medicine, National Hospital Organization Kanazawa Medical Center, Ishikawa, Japan. naika-k1@kinbyou.hosp.go.jp
Fujimura
Masaki
M
Myou
Shigeharu
S
Watanabe
Kazuyoshi
K
Waseda
Yuko
Y
Nakao
Shinji
S
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
C106878:KF 19514; D009287:Naphthyridines; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010047:Ovalbumin; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D000109:Acetylcholine; D006909:Hydroxyproline