Upregulation of phosphodiesterase-4 in the lung of allergic rats.

Abstract

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.

• Authors: Hui-Fang Tang, Yan-Hua Song, Jun-Chun Chen, Ji-Qiang Chen, Peng Wang
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 171 Issue 8 Pg. 823-8 (Apr 15 2005) ISSN: 1073-449X [Print] United States
• PMID: 15665325 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• RNA, Messenger
• Interleukin-4
• Dexamethasone
• Ovalbumin
• 3',5'-Cyclic-AMP Phosphodiesterases
• Cyclic Nucleotide Phosphodiesterases, Type 4
• Rolipram

Topics

• 3',5'-Cyclic-AMP Phosphodiesterases (genetics)
• Airway Resistance (genetics, immunology)
• Animals
• Asthma (genetics, immunology)
• Cyclic Nucleotide Phosphodiesterases, Type 4
• Dexamethasone (pharmacology)
• Interleukin-4 (metabolism)
• Lung (immunology)
• Male
• Ovalbumin (immunology)
• RNA, Messenger (genetics)
• Rats
• Rats, Sprague-Dawley
• Respiratory Hypersensitivity (genetics, immunology)
• Rolipram (pharmacology)
• Trachea (drug effects, immunology)
• Up-Regulation (genetics)