Upregulation of phosphodiesterase-4 in the lung of allergic rats.
Inhibitors of phosphodiesterase-4 (PDE4) are efficacious for allergic asthma in animal models and have shown some efficacy in human asthma. Regulation of PDE4 in allergy and asthma has been widely investigated in blood leukocytes, with discrepant results. This study investigated PDE4 regulation in the lung in a rat model of allergic asthma. Ovalbumin sensitization and challenge significantly increased pulmonary resistance and lung interleukin (IL)-4 production. The increases in pulmonary resistance and IL-4 production were both suppressed by the PDE4-selective inhibitor rolipram or the corticosteroid drug dexamethasone. Furthermore, cAMP-PDE enzyme activity in the lung was also significantly increased by the sensitization and challenge. mRNA analysis confirmed that PDE4 gene expression was increased in the lung of the allergic rats. A highly significant correlation was observed between the increases in PDE activity and IL-4 production. Our data suggest, for the first time, that PDE4 may be upregulated in the lung and play a role in the pathogenesis of allergic asthma.
Tang
Hui-Fang
HF
Schering-Plough Research Institute, 2015 Galloping Hill Road, K-15-1600, Kenilworth, NJ 07033, USA.
Song
Yan-Hua
YH
Chen
Jun-Chun
JC
Chen
Ji-Qiang
JQ
Wang
Peng
P
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics*; D000403:Airway Resistance / Q000235:genetics / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D003907:Dexamethasone / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism; D008168:Lung / Q000276:immunology*; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology*; D020889:Rolipram / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics
D012333:RNA, Messenger; D015847:Interleukin-4; D003907:Dexamethasone; D010047:Ovalbumin; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram