Phosphodiesterase expression in human epithelial cells.
Epithelial cells play a critical role in airway inflammation and have the capacity to produce many inflammatory mediators, including bioactive lipids and proinflammatory cytokines. Intracellular levels of cAMP and cGMP are important in the control of inflammatory cell function. These cyclic nucleotides are inactivated via a family of phosphodiesterase (PDE) enzymes, providing a possible site for drug intervention in chronic inflammatory conditions. We studied the expression of PDE activity in an epithelial cell line (A549) and in primary human airway epithelial cells (HAECs). We measured PDE function using specific inhibitors to identify the PDE families present and used RT-PCR to elucidate the expression of PDE isogenes. Both A549 cells and HAECs predominantly expressed PDE4 activity, with lesser PDE1, PDE3, and PDE5 activity. RT-PCR identified HSPDE4A5 and HSPDE4D3 together with HSPDE7. Inhibition of PDE4 and PDE3 reduced secretion by these cells. Epithelial PDE may be an important target for PDE4 inhibitors in the development of the control of asthmatic inflammation, particularly when delivered via the inhaled route.
Wright
L C
LC
Department of Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London SW3 6LY, United Kingdom.
Seybold
J
J
Robichaud
A
A
Adcock
I M
IM
Barnes
P J
PJ
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics* / Q000378:metabolism; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000201:enzymology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020889:Rolipram; D013876:Thiophenes / Q000494:pharmacology
D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D011760:Pyrrolidinones; D013876:Thiophenes; C097915:Org 9935; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C011145:zaprinast; D020889:Rolipram; D015056:1-Methyl-3-isobutylxanthine