Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases.
Adenosine, a nucleoside derived primarily from the extracellular hydrolysis of adenine nucleotides, is a potent regulator of inflammation. Adenosine mediates its effects on inflammatory cells by engaging one or more cell-surface receptors. The expression and function of adenosine receptors on different cell types change during the course of rheumatic diseases, such as rheumatoid arthritis (RA). Targeting adenosine receptors directly for the treatment of rheumatic diseases is currently under study; however, indirect targeting of adenosine receptors by enhancing adenosine levels at inflamed sites accounts for most of the anti-inflammatory effects of methotrexate, the anchor drug for the treatment of RA. In this Review, we discuss the regulation of extracellular adenosine levels and the role of adenosine in regulating the inflammatory and immune responses in rheumatic diseases such as RA, psoriasis and other types of inflammatory arthritis. In addition, adenosine and its receptors are involved in promoting fibrous matrix production in the skin and other organs, and the role of adenosine in fibrosis and fibrosing diseases is also discussed.
NYU-HHC Clinical and Translational Science Institute, NYU School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Bruce N
BN
Cronstein
New England Inflammation and Tissue Protection Institute, Northeastern University, 360 Huntington Avenue, 312 MU, Boston, Massachusetts 02115, USA.
Michail
M
Sitkovsky
D056704:Adaptive Immunity; D000241:Adenosine / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D018501:Antirheumatic Agents / Q000494:pharmacology; D005355:Fibrosis; D018628:Gene Dosage; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000378:metabolism*; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012216:Rheumatic Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D000241:Adenosine