| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Respiratory Diseases Area, Novartis Institutes for BioMedical Research, Horsham, West Sussex, United Kingdom
2 Department of Molecular Phamacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Scotland, United Kingdom
3 Informatics and Knowledge Management, Novartis Institutes for BioMedical Research, Basle, Switzerland
4 Department of Medicine, University of Glasgow, Glasgow, United Kingdom
5 The Unit for Lung Investigations, Institute of Experimental and Clinical Medicine, Tallinn, Estonia
* To whom correspondence should be addressed. E-mail: gino.van_heeke{at}pharma.novartis.com.
The expression profile of a panel of 15 cyclic AMP phosphodiesterase isoforms was determined for inflammatory cell types of relevance to Chronic Obstructive Pulmonary Disease (COPD). In particular, the expression profiles for bronchoalveolar macrophages, peripheral blood monocytes, T-lymphocytes and neutrophils from smokers with and without COPD were compared. The phosphodiesterase expression profile was also analyzed for peripheral blood monocytes, T-lymphocytes and neutrophils from non-smokers and compared with smokers. Qualitative RT-PCR identified transcripts for PDE4A10, PDE4A7, PDE4B1, PDE4B2, PDE4D1 and PDE4D2 isoforms, as well as transcripts for both PDE3B and PDE7A, in T-cells, monocytes and macrophages in all subjects. Transcripts for PDE4B3 and PDE4D4 were not observed in any of the cell types investigated. PDE4C was detected in all cells analyzed except for T-cells. The long PDE4A4, PDE4D3 and PDE4D5 isoforms exhibited cell-type specific expression patterns. Semi-quantitative and real-time quantitative RT-PCR was used to analyze differential expression between disease states and between cell types. PDE4A4 was found significantly up-regulated in lung macrophages from smokers with COPD when compared to control smokers. Further, PDE4A4 as well as PDE4B2 transcripts were detected in higher amounts in peripheral blood monocytes of smokers when compared to non-smokers. Finally, PDE4D5 and PDE4C were differentially regulated in lung macrophages when compared to monocytes of the same subjects, irrespective of the disease state. The data obtained suggest that PDE4A4 may be relevant as a macrophage-specific anti-inflammatory target for COPD.
This article has been cited by other articles:
|
|
 |
|
  B. D. Sachs, G. S. Baillie, J. R. McCall, M. A. Passino, C. Schachtrup, D. A. Wallace, A. J. Dunlop, K. F. MacKenzie, E. Klussmann, M. J. Lynch, et al. p75 neurotrophin receptor regulates tissue fibrosis through inhibition of plasminogen activation via a PDE4/cAMP/PKA pathway J. Cell Biol., July 30, 2007; 177(6): 1119 - 1132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Omori and J. Kotera Overview of PDEs and Their Regulation Circ. Res., February 16, 2007; 100(3): 309 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Y. Meliton, N. M. Munoz, A. Lambertino, E. Boetticher, J. Learoyd, X. Zhu, and A. R. Leff Phosphodiesterase 4 inhibition of {beta}2-integrin adhesion caused by leukotriene B4 and TNF-{alpha} in human neutrophils Eur. Respir. J., November 1, 2006; 28(5): 920 - 928. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ishii, A. M. Wallace, X. Zhang, J. Gosselink, R. T. Abboud, J. C. English, P. D. Pare, and A. J. Sandford Stability of housekeeping genes in alveolar macrophages from COPD patients Eur. Respir. J., February 1, 2006; 27(2): 300 - 306. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
