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Published ahead of print on January 21, 2005, doi:10.1164/rccm.200406-771OC

Am. J. Respir. Crit. Care Med., Volume 171, Number 8, April 2005, 823-828

A more recent version of this article appeared on April 15, 2005
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Submitted on June 17, 2004
Accepted on January 14, 2005

Upregulation of Phosphodiesterase-4 in the Lung of Allergic Rats

Hui-Fang Tang1, Yan-Hua Song1, Jun-Chun Chen1, Ji-Qiang Chen2, and Peng Wang2*

1 Department of Inflammation and Infection, Zhejiang Respiratory Drugs Research Laboratory of State Food & Drugs Administration of China and Zhejiang University School of Medicine, Hangzhou, Zhejiang, China, 2 Department of Inflammation and Infection, Zhejiang Respiratory Drugs Research Laboratory of State Food & Drugs Administration of China and Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Schering-Plough Research Institute, Kenilworth, NJ, USA

* To whom correspondence should be addressed. E-mail: peng.wang{at}spcorp.com.

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. In this study, we 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. Interestingly, 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.
Key words: Phosphodiesterase-4, PDE4, cAMP, asthma, rat




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