The role of PDE4 in pulmonary inflammation and goblet cell hyperplasia in allergic rats.
Phosphodiesterase 4 (PDE4) has been suggested to a critical factor in the pathogenesis of inflammation by metabolizing cAMP in human leukocytes, endothelium and epithelium. The present study aimed at evaluating the PDE4 activity and expression, the relationship between the inflammation and cAMP- activity in the lungs, and potential interventions of PDE inhibitors and antiinflammatory drugs in the reduction of lung inflammation and goblet cell hyperplasia in allergic rats. The total leukocyte number and eosinophil number in bronchoalveolar lavegar fluid and infiltration of inflammatory cells in the perivascular and peribronchial spaces, structure changes and goblet cell hyperplasia in the OVA-sensitized and challenged allergic rats. A significant correlation was observed between the increases in cAMP-PDE activity and inflammation in the lung. Those OVA-induced changes were prevented by pretreatment with PDE inhibitor in a dose-related patterns and with glucocorticosteriod. We found an increase in the proportion of PDE4 and PDE4 gene expression, while a decrease in the proportion of PDE3 in the lung of the allergic rats. Incubation with different PDE inhibitors down-regulated OVA-induced cAMP hydrolysis. Our data suggest that PDE4C may play an important role in the airway inflammation, remodeling and goblet cell hyperplasia after repeated challenge of sensitized rats.
Zhejiang Respiratory Drugs Research Laboratory of State Foods and Drugs Administration of China, Medical School of Zhejiang University, Hangzhou 310031, China.
Hui-Fang
HF
Tang
Ji-Qiang
JQ
Chen
Qiang-Min
QM
Xie
Xu-Yang
XY
Zheng
Yi-Liang
YL
Zhu
Ian
I
Adcock
Xiangdong
X
Wang
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002452:Cell Count; D000242:Cyclic AMP / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D005786:Gene Expression Regulation; D020397:Goblet Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D006965:Hyperplasia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006967:Hypersensitivity / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D008297:Male; D011014:Pneumonia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517361:PDE4C protein, human