help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on July 10, 2003, doi:10.1165/rcmb.2003-0118OC

Am. J. Respir. Cell Mol. Biol., Volume 30, Number 1, January 2004, 118-125

A more recent version of this article appeared on January 1, 2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2003-0118OCv1
30/1/118    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhong, H.
Right arrow Articles by Zeng, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhong, H.
Right arrow Articles by Zeng, D.

Submitted on April 1, 2003
Revised on July 10, 2003

A2B Adenosine Receptors Increase Cytokine Release by Bronchial Smooth Muscle Cells

Hongyan Zhong1, Luiz Belardinelli1, Tenning Maa1, Igor Feoktistov2, Italo Biaggioni2, and Dewan Zeng1*

1 Department of Drug Research and Pharmacological Sciences, CV Therapeutics, Inc., Palo Alto, CA, USA, 2 Department of Medicine and Pharmacology, Vanderbilt University, Nashville, TN, USA

* To whom correspondence should be addressed. E-mail: Dewan.Zeng{at}cvt.com.

Adenosine (Ado) has been suggested to play a role in inflammatory airway diseases such as asthma and COPD. The goal of this study was to determine the effect of Ado and its receptor subtypes on cytokine release by BSMCs. The A2B AdoR was expressed at the highest level among the four AdoR subtypes. Activation of the A2B AdoR by an Ado analog, NECA, increased cAMP accumulation with potency (EC50 value) of 21.2±0.2µM. The effect of NECA on the expression of the inflammatory cytokines was determined using a complementary DNA (cDNA) array consisting of 23 cytokine genes and confirmed using real-time RT-PCR and ELISA. NECA increased the release of IL-6 and MCP-1 proteins with EC50 values of 1.26±0.25µM and 0.40±0.08 µM, respectively, and the maximal folds of induction were 20.8±1.7 and 6.4±0.7 fold, respectively. Selective agonists for the A1, A2A, and A3 AdoR subtypes had no effect on cytokine release. The effects of NECA were attenuated by selective antagonists of the A2B AdoR. Thus, Ado increases the release of IL-6 and MCP-1 from BSMCs via activation of the A2B AdoR. Our findings provide a novel mechanism whereby adenosine acts as a proinflammatory mediator in the airway.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
S. Ryzhov, R. Zaynagetdinov, A. E. Goldstein, S. V. Novitskiy, M. M. Dikov, M. R. Blackburn, I. Biaggioni, and I. Feoktistov
Effect of A2B Adenosine Receptor Gene Ablation on Proinflammatory Adenosine Signaling in Mast Cells
J. Immunol., June 1, 2008; 180(11): 7212 - 7220.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. Ryzhov, R. Zaynagetdinov, A. E. Goldstein, S. V. Novitskiy, M. R. Blackburn, I. Biaggioni, and I. Feoktistov
Effect of A2B Adenosine Receptor Gene Ablation on Adenosine-Dependent Regulation of Proinflammatory Cytokines
J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 694 - 700.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. Mohsenin, T. Mi, Y. Xia, R. E. Kellems, J.-F. Chen, and M. R. Blackburn
Genetic removal of the A2A adenosine receptor enhances pulmonary inflammation, mucin production, and angiogenesis in adenosine deaminase-deficient mice
Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L753 - L761.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. J. Mustafa, A. Nadeem, M. Fan, H. Zhong, L. Belardinelli, and D. Zeng
Effect of a Specific and Selective A2B Adenosine Receptor Antagonist on Adenosine Agonist AMP and Allergen-Induced Airway Responsiveness and Cellular Influx in a Mouse Model of Asthma
J. Pharmacol. Exp. Ther., March 1, 2007; 320(3): 1246 - 1251.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
H. Zhong, Y. Wu, L. Belardinelli, and D. Zeng
A2B Adenosine Receptors Induce IL-19 from Bronchial Epithelial Cells, Resulting in TNF-{alpha} Increase
Am. J. Respir. Cell Mol. Biol., November 1, 2006; 35(5): 587 - 592.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
M. F. Ethier and J. M. Madison
Adenosine A1 Receptors Mediate Mobilization of Calcium in Human Bronchial Smooth Muscle Cells
Am. J. Respir. Cell Mol. Biol., October 1, 2006; 35(4): 496 - 502.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
C. D. Douillet, W. P. Robinson III, P. M. Milano, R. C. Boucher, and P. B. Rich
Nucleotides induce IL-6 release from human airway epithelia via P2Y2 and p38 MAPK-dependent pathways
Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L734 - L746.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
L. M. Kreckler, T. C. Wan, Z.-D. Ge, and J. A. Auchampach
Adenosine Inhibits Tumor Necrosis Factor-{alpha} Release from Mouse Peritoneal Macrophages via A2A and A2B but Not the A3 Adenosine Receptor
J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 172 - 180.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. Roman, H. N. Rivera, S. Roser-Page, S. V. Sitaraman, and J. D. Ritzenthaler
Adenosine induces fibronectin expression in lung epithelial cells: implications for airway remodeling
Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L317 - L325.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
S. Gessi, K. Varani, S. Merighi, E. Cattabriga, C. Pancaldi, Y. Szabadkai, R. Rizzuto, K.-N. Klotz, E. Leung, S. Mac Lennan, et al.
Expression, Pharmacological Profile, and Functional Coupling of A2B Receptors in a Recombinant System and in Peripheral Blood Cells Using a Novel Selective Antagonist Radioligand, [3H]MRE 2029-F20
Mol. Pharmacol., June 1, 2005; 67(6): 2137 - 2147.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
H. Zhong, L. Belardinelli, T. Maa, and D. Zeng
Synergy between A2B Adenosine Receptors and Hypoxia in Activating Human Lung Fibroblasts
Am. J. Respir. Cell Mol. Biol., January 1, 2005; 32(1): 2 - 8.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
C. D. Douillet, W. P. Robinson III, B. L. Zarzaur, E. R. Lazarowski, R. C. Boucher, and P. B. Rich
Mechanical Ventilation Alters Airway Nucleotides and Purinoceptors in Lung and Extrapulmonary Organs
Am. J. Respir. Cell Mol. Biol., January 1, 2005; 32(1): 52 - 58.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
I. Feoktistov, S. Ryzhov, H. Zhong, A. E. Goldstein, A. Matafonov, D. Zeng, and I. Biaggioni
Hypoxia Modulates Adenosine Receptors in Human Endothelial and Smooth Muscle Cells Toward an A2B Angiogenic Phenotype
Hypertension, November 1, 2004; 44(5): 649 - 654.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2003 American Thoracic Society. 		  2009 ATS Conference