Role and Function of A2A and A₃ Adenosine Receptors in Patients with Ankylosing Spondylitis, Psoriatic Arthritis and Rheumatoid Arthritis.
Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are chronic inflammatory rheumatic diseases that affect joints, causing debilitating pain and disability. Adenosine receptors (ARs) play a key role in the mechanism of inflammation, and the activation of A2A and A₃AR subtypes is often associated with a reduction of the inflammatory status. The aim of this study was to investigate the involvement of ARs in patients suffering from early-RA (ERA), RA, AS and PsA. Messenger RNA (mRNA) analysis and saturation binding experiments indicated an upregulation of A2A and A₃ARs in lymphocytes obtained from patients when compared with healthy subjects. A2A and A₃AR agonists inhibited nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activation and reduced inflammatory cytokines release, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6. Moreover, A2A and A₃AR activation mediated a reduction of metalloproteinases (MMP)-1 and MMP-3. The effect of the agonists was abrogated by selective antagonists demonstrating the direct involvement of these receptor subtypes. Taken together, these data confirmed the involvement of ARs in chronic autoimmune rheumatic diseases highlighting the possibility to exploit A2A and A₃ARs as therapeutic targets, with the aim to limit the inflammatory responses usually associated with RA, AS and PsA.
['Ravani|Annalisa|A|', 'Vincenzi|Fabrizio|F|', 'Bortoluzzi|Alessandra|A|', 'Padovan|Melissa|M|', 'Pasquini|Silvia|S|', 'Gessi|Stefania|S|', 'Merighi|Stefania|S|', 'Borea|Pier Andrea|PA|', 'Govoni|Marcello|M|', 'Varani|Katia|K|']
D000241:Adenosine D058908:Adenosine A2 Receptor Agonists D058917:Adenosine A2 Receptor Antagonists D058909:Adenosine A3 Receptor Agonists D058918:Adenosine A3 Receptor Antagonists D015535:Arthritis, Psoriatic D001172:Arthritis, Rheumatoid D016022:Case-Control Studies D016207:Cytokines D005260:Female D006801:Humans D007700:Kinetics D008214:Lymphocytes D008297:Male D020781:Matrix Metalloproteinase 1 D019278:Matrix Metalloproteinase 3 D008875:Middle Aged D016328:NF-kappa B D010627:Phenethylamines D011720:Pyrazoles D011743:Pyrimidines D012333:RNA, Messenger D043705:Receptor, Adenosine A2A D043684:Receptor, Adenosine A3 D013167:Spondylitis, Ankylosing
adenosine receptors ankylosing spondylitis psoriatic arthritis rheumatoid arthritis inflammation