A(2A) and A(3) adenosine receptor expression in rheumatoid arthritis: upregulation, inverse correlation with disease activity score and suppression of inflammatory cytokine and metalloproteinase release

作者：Varani Katia; Padovan Melissa; Vincenzi Fabrizio; Targa Martina; Trotta Francesco; Govoni Marcello; Borea Pier Andrea^*

来源：Arthritis Research and Therapy, 2011, 13(6): R197.

DOI：10.1186/ar3527

Introduction: The reduction of the inflammatory status represents one of the most important targets in rheumatoid arthritis (RA). A central role of A(2A) and A(3) adenosine receptors (ARs) in mechanisms of inflammation has been reported in different pathologies. The primary aim of this study was to investigate the A(2A) and A(3)ARs and their involvement in RA progression measured by Disease Activity Score in 28 or 44 joints (DAS28 or DAS).
Methods: ARs were analyzed by saturation binding assays, mRNA and Western blotting analysis in lymphocytes from early and established RA patients. The effect of A(2A) and A(3)AR agonists in nuclear factor kB (NF-kB) pathway was evaluated. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) release was carried out by A(2A) and A(3)AR activation. AR pharmacological regulation in matrix metalloproteinase-1 (MMP-1) and metalloproteinase-3 (MMP-3) release was also studied.
Results: In lymphocytes obtained from RA patients, A(2A) and A(3)ARs were up-regulated if compared with healthy controls. A(2A) and A3AR activation inhibited the NF-kB pathway and diminished inflammatory cytokines such as TNF-alpha, IL-1 beta and IL-6. A(2A) and A(3)AR agonists mediated a reduction of MMP-1 and MMP-3 release. A(2A) and A(3)AR density inversely correlated with DAS28 and DAS suggesting a direct role of the endogenous activation of these receptors in the control of RA joint inflammation.
Conclusions: Taken together these data demonstrate that the inflammatory and clinical responses in RA are regulated by A(2A) and A(3)ARs and support the use of A(2A) and/or A(3)AR agonists as novel and effective pharmacological treatment in RA patients.

• 出版日期2011