| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Laboratory of Pneumology, Unit of Respiratory Pharmacology, Leuven, Belgium
CORRESPONDENCE: G.M. Verleden, Dept of Pneumology, UZ Gasthuisberg, 49 Herestraat, Leuven, B-3000, Belgium. Fax: 32 16346803. E-mail: geert.verleden@uz.kuleuven.ac.be
Keywords: cyclic adenosine monophosphate, cyclic adenosine monophosphate-dependent protein kinase, human airway smooth muscle cells, interleukin-1ß
Received: December 3, 2002
Accepted April 15, 2003
W.A. Wuyts is a research fellow of the Fonds voor wetenschappelijk onderzoek Vlaanderen. This study was funded by the Fonds voor wetenschappelijk onderzoek Vlaanderen G 0220.99. G.M. Verleden is a holder of the GSK Chair for pulmonary pharmacology at the Katholieke Universiteit Leuven.
Inflammatory cells, such as eosinophils, seem to be key players in the inflammatory process of asthma. These cells are attracted by chemokines, for example eotaxin and monocyte chemotactic protein (MCP-1).
In this study, the authors investigated whether eotaxin and MCP-1 expression and release in human airway smooth muscle cells could be modulated by an increase in intracellular cyclic adenosine monophosphate (cAMP) concentration. The possible involvement of cAMP-dependent protein kinase A (PKA) was also studied.
Forskolin, a direct stimulator of adenylyl cyclase, decreased the interleukin (IL)-1ß-induced eotaxin and MCP-1 release by 73±8 and 65±6%, respectively. 8Bromo-cAMP, a cAMP analogue, similarly decreased the chemokine production by 58±9 and 63±8% for eotaxin and MCP-1, respectively. Prostaglandin E2, known as an activator of the prostanoid receptors EP2 and EP4, which are positively coupled to adenylyl cyclase, also decreased the IL-1ß-induced eotaxin and MCP-1 production by 57±17 and 53±4%, respectively. H-89, an inhibitor of PKA, was able to inhibit the decrease in eotaxin and MCP-1 protein release induced by forskolin. Using Western-blot analysis, no effect of cAMP was found on the IL-1ß-induced p38 mitogen-activated protein kinase, extracellular signal-related kinase or cJun N-terminal kinase activation.
This study shows that an increase in intracellular cyclic adenosine monophosphate concentration may decrease the interleukin-1ß-induced eotaxin and monocyte chemotactic protein-1 expression and production. This can be inhibited by addition of H-89, an inhibitor of cyclic adenosine monophosphate-dependent protein kinase. No decrease was observed in interleukin-1ß-induced p38 mitogen-activated protein kinase, extracellular signal-related kinase or cJun N-terminal kinase activation. These findings may be important for the further development of new anti-inflammatory drugs.
This article has been cited by other articles:
|
|
 |
|
  M. A. Punchard, A. O. Pozzi, T. P. de Prada, M. T. Coronado, P. Gonzalez, and P. Fantidis Letter to the Editor: Monocyte cAMP Content Is Decreased in Patients With Stable Angina Arterioscler. Thromb. Vasc. Biol., February 1, 2007; 27(2): 436 - 437. [Full Text] [PDF]
|
|
|
|
 |
|
 W. Li, T. Wang, C. Ma, T. Xiong, Y. Zhu, and X. Wang Calcitonin gene-related peptide inhibits interleukin-1beta-induced endogenous monocyte chemoattractant protein-1 secretion in type II alveolar epithelial cells Am J Physiol Cell Physiol, September 1, 2006; 291(3): C456 - C465. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kanefsky, M. Lenburg, and C.-M. Hai Cholinergic Receptor and Cyclic Stretch-Mediated Inflammatory Gene Expression in Intact ASM Am. J. Respir. Cell Mol. Biol., April 1, 2006; 34(4): 417 - 425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nie, L. Corbett, A. J. Knox, and L. Pang Differential Regulation of Chemokine Expression by Peroxisome Proliferator-activated Receptor {gamma} Agonists: INTERACTIONS WITH GLUCOCORTICOIDS AND {beta}2-AGONISTS J. Biol. Chem., January 28, 2005; 280(4): 2550 - 2561. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
