About this Journal Submit a Manuscript Table of Contents
TheScientificWorldJOURNAL
Volume 11 (2011), Pages 320-339
http://dx.doi.org/10.1100/tsw.2011.22
Review Article

Anti-Inflammatory and Immunosuppressive Effects of the A2A Adenosine Receptor

Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Scotland

Received 15 October 2010; Revised 10 December 2010; Accepted 17 December 2010

Academic Editor: Mauro Perretti

Copyright © 2011 Gillian R. Milne and Timothy M. Palmer.

Abstract

The production of adenosine represents a critical endogenous mechanism for regulating immune and inflammatory responses during conditions of stress, injury, or infection. Adenosine exerts predominantly protective effects through activation of four 7-transmembrane receptor subtypes termed A1, A2A, A2B, and A3, of which the A2A adenosine receptor (A2AAR) is recognised as a major mediator of anti-inflammatory responses. The A2AAR is widely expressed on cells of the immune system and numerous in vitro studies have identified its role in suppressing key stages of the inflammatory process, including leukocyte recruitment, phagocytosis, cytokine production, and immune cell proliferation. The majority of actions produced by A2AAR activation appear to be mediated by cAMP, but downstream events have not yet been well characterised. In this article, we review the current evidence for the anti-inflammatory effects of the A2AAR in different cell types and discuss possible molecular mechanisms mediating these effects, including the potential for generalised suppression of inflammatory gene expression through inhibition of the NF-κB and JAK/STAT proinflammatory signalling pathways. We also evaluate findings from in vivo studies investigating the role of the A2AAR in different tissues in animal models of inflammatory disease and briefly discuss the potential for development of selective A2AAR agonists for use in the clinic to treat specific inflammatory conditions.