HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Khoa, N. D. Articles by Cronstein, B. N. Search for Related Content PubMed PubMed Citation Articles by Khoa, N. D. Articles by Cronstein, B. N.

Th1 Cytokines Regulate Adenosine Receptors and Their Downstream Signaling Elements in Human Microvascular Endothelial Cells ¹

Divisions of Clinical Pharmacology and Rheumatology, Department of Medicine, New York University School of Medicine, New York, NY 10016

We and others have shown that adenosine, acting at its receptors, is a potent modulator of inflammation and angiogenesis. To better understand the regulation of adenosine receptors during these processes we studied the effects of IL-1, TNF-, and IFN- on expression and function of adenosine receptors and select members of their coupling G proteins in human dermal microvascular endothelial cells (HMVEC). HMVEC expressed message and protein for A_2A and A_2B, but not A₁ or A₃ receptors. IL-1 and TNF- treatment increased message and protein expression of A_2A and A_2B receptor. IFN- treatment also increased the expression of A_2B receptors, but decreased expression of A_2A receptors. Resting HMVEC and IFN--treated cells showed minimal cAMP response to the selective A_2A receptor agonist 2-[2-(4-chlorophenyl)ethoxy]adenosine (MRE0094). In contrast, MRE0094 stimulated a dose-dependent increase in cAMP levels in TNF--treated cells that was almost completely blocked by the A_2A receptor antagonist ZM-241385 (4-{2-[7-amino-2-(2-furyl)[1,2,4]triazolo-[2,3-a][1,3,5]triazin-5-ylamino]ethyl}phenol). The nonselective adenosine receptor agonist 5'-(N-ethylcarboxamido)adenosine increased cAMP levels in both TNF-- and IFN--treated cells, but not control cells, and its effect was only partially reversed by ZM-241385 in TNF--treated cells and not affected in IFN--treated cells. HMVEC expressed a higher level of G protein 1 isoform than 4 isoform. Although none of the cytokines tested affected G₁ expression, both IL-1 and TNF- significantly up-regulated G₄ expression. These findings indicate that inflammatory cytokines modulate adenosine receptor expression and function on HMVECs and suggest that the interaction between proinflammatory cytokines and adenosine receptors may affect therapeutic responses to anti-inflammatory drugs that act via adenosine-dependent mechanisms.

This article has been cited by other articles:

				C. van der Putten, E. A. Zuiderwijk-Sick, L. van Straalen, E. D. de Geus, L. A. Boven, I. Kondova, A. P. IJzerman, and J. J. Bajramovic Differential Expression of Adenosine A3 Receptors Controls Adenosine A2A Receptor-Mediated Inhibition of TLR Responses in Microglia J. Immunol., June 15, 2009; 182(12): 7603 - 7612. [Abstract] [Full Text] [PDF]

				M. Katebi, M. Soleimani, and B. N. Cronstein Adenosine A2A receptors play an active role in mouse bone marrow-derived mesenchymal stem cell development J. Leukoc. Biol., March 1, 2009; 85(3): 438 - 444. [Abstract] [Full Text] [PDF]

				T. Hasegawa, D. Bouis, H. Liao, S. H. Visovatti, and D. J. Pinsky Ecto-5' Nucleotidase (CD73)-Mediated Adenosine Generation and Signaling in Murine Cardiac Allograft Vasculopathy Circ. Res., December 5, 2008; 103(12): 1410 - 1421. [Abstract] [Full Text] [PDF]

				S. Kreth, C. Ledderose, I. Kaufmann, G. Groeger, and M. Thiel Differential expression of 5'-UTR splice variants of the adenosine A2A receptor gene in human granulocytes: identification, characterization, and functional impact on activation FASEB J, September 1, 2008; 22(9): 3276 - 3286. [Abstract] [Full Text] [PDF]

				D. van der Hoeven, T. C. Wan, and J. A. Auchampach Activation of the A3 Adenosine Receptor Suppresses Superoxide Production and Chemotaxis of Mouse Bone Marrow Neutrophils Mol. Pharmacol., September 1, 2008; 74(3): 685 - 696. [Abstract] [Full Text] [PDF]

				G. E. Garcia, L. D. Truong, P. Li, P. Zhang, J. Du, J.-F. Chen, and L. Feng Adenosine A2A receptor activation and macrophage-mediated experimental glomerulonephritis FASEB J, February 1, 2008; 22(2): 445 - 454. [Abstract] [Full Text] [PDF]

				Y. Fang and M. E. Olah Cyclic AMP-Dependent, Protein Kinase A-Independent Activation of Extracellular Signal-Regulated Kinase 1/2 Following Adenosine Receptor Stimulation in Human Umbilical Vein Endothelial Cells: Role of Exchange Protein Activated by cAMP 1 (Epac1) J. Pharmacol. Exp. Ther., September 1, 2007; 322(3): 1189 - 1200. [Abstract] [Full Text] [PDF]

				J. Reutershan, R. E. Cagnina, D. Chang, J. Linden, and K. Ley Therapeutic Anti-Inflammatory Effects of Myeloid Cell Adenosine Receptor A2a Stimulation in Lipopolysaccharide-Induced Lung Injury J. Immunol., July 15, 2007; 179(2): 1254 - 1263. [Abstract] [Full Text] [PDF]

				S. Morello, K. Ito, S. Yamamura, K.-Y. Lee, E. Jazrawi, P. DeSouza, P. Barnes, C. Cicala, and I. M. Adcock IL-1beta and TNF-{alpha} Regulation of the Adenosine Receptor (A2A) Expression: Differential Requirement for NF-{kappa}B Binding to the Proximal Promoter J. Immunol., November 15, 2006; 177(10): 7173 - 7183. [Abstract] [Full Text] [PDF]

				N. D. Khoa, M. Postow, J. Danielsson, and B. N. Cronstein Tumor Necrosis Factor-{alpha} Prevents Desensitization of G{alpha}s-Coupled Receptors by Regulating GRK2 Association with the Plasma Membrane Mol. Pharmacol., April 1, 2006; 69(4): 1311 - 1319. [Abstract] [Full Text] [PDF]

				A. Fortin, D. Harbour, M. Fernandes, P. Borgeat, and S. Bourgoin Differential expression of adenosine receptors in human neutrophils: up-regulation by specific Th1 cytokines and lipopolysaccharide J. Leukoc. Biol., March 1, 2006; 79(3): 574 - 585. [Abstract] [Full Text] [PDF]

				J. L. Chunn, A. Mohsenin, H. W. J. Young, C. G. Lee, J. A. Elias, R. E. Kellems, and M. R. Blackburn Partially adenosine deaminase-deficient mice develop pulmonary fibrosis in association with adenosine elevations Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L579 - L587. [Abstract] [Full Text] [PDF]

				A. Desai, C. Victor-Vega, S. Gadangi, M. C. Montesinos, C. C. Chu, and B. N. Cronstein Adenosine A2A Receptor Stimulation Increases Angiogenesis by Down-Regulating Production of the Antiangiogenic Matrix Protein Thrombospondin 1 Mol. Pharmacol., May 1, 2005; 67(5): 1406 - 1413. [Abstract] [Full Text] [PDF]

				W. A. Sands, A. F. Martin, E. W. Strong, and T. M. Palmer Specific Inhibition of Nuclear Factor-{kappa}B-Dependent Inflammatory Responses by Cell Type-Specific Mechanisms upon A2A Adenosine Receptor Gene Transfer Mol. Pharmacol., November 1, 2004; 66(5): 1147 - 1159. [Abstract] [Full Text] [PDF]