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.
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Effects of KF19514, a phosphodiesterase 4 and 1 Inhibitor, on bronchial inflammation and remodeling in a murine model of chronic asthma.
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Department of Respiratory Medicine, National Hospital Organization Kanazawa Medical Center, Ishikawa, Japan.
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.
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Pharmaceutical Research Center, Kyowa Hakko Kogyo Co., Ltd., 1188 Shimotogari, Nagaizumi, Shizuoka, 411-8731, Japan.
We employed an ex vivo [(3)H]rolipram binding experiment to elucidate the mechanism of emetic activity of phosphodiesterase 4 inhibitors. In Suncus murinus (an insectivore used for evaluation of emesis), emetic potential as well as ability to occupy the high-affinity rolipram binding site in brain membrane fraction in vivo were determined for phosphodiesterase 4 inhibitors. In vitro, [(3)H]rolipram bound to the membrane fraction of S.
View Article and Find Full Text PDFKF19514, a phosphodiesterase 4 and 1 inhibitor, inhibits TNF-alpha-induced GM-CSF production by a human bronchial epithelial cell line via inhibition of PDE4.
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Clin Exp Allergy
May 2000
The Third Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Ishikawa, Japan.
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