Targeting G protein-coupled A2a adenosine receptors to engineer inflammation in vivo.
G protein-coupled adenosine receptors are the subject of intense study as immunomodulators of inflammation especially since the recent demonstration that the A2a receptor acts to down-regulate inflammation and inhibit tissue damage in vivo [Nature 414 (6866) (2001) 916]. The adverse effects of overactive inflammation are evident in diseases e.g. sepsis, rheumatoid arthritis, and multiple sclerosis underscoring the importance of inhibiting inflammation or selectively enhancing inflammatory processes. It has been shown recently that the A2a adenosine receptor is a critical component of an endogenous "immunosuppressive loop" in which extracellular adenosine that accumulates due to local hypoxia caused by inflammatory insult signals through cAMP-elevating A2a receptors in a delayed negative feedback manner. Understanding how tissues regulate inflammation will provide the information necessary to allow for the engineering, or selective targeting, of endogenous inflammatory pathways. Recognition of A2a receptors as "natural" or endogenous brakes of inflammation provides the intellectual scaffolding needed to pursue these goals.
Gomez
Gregorio
G
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10/11N311, 10 Center Drive-MSC 1892, Bethesda, MD 20892-1892, USA.
Sitkovsky
Michail V
MV
D000818:Animals; D000242:Cyclic AMP / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D019204:GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007165:Immunosuppression Therapy; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018047:Receptors, Purinergic P1 / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D018836:Inflammation Mediators; D018047:Receptors, Purinergic P1; D000242:Cyclic AMP; D019204:GTP-Binding Proteins