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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 6/2011

Open Access 01-12-2011 | Research article

A2A and A3 adenosine receptor expression in rheumatoid arthritis: upregulation, inverse correlation with disease activity score and suppression of inflammatory cytokine and metalloproteinase release

Authors: Katia Varani, Melissa Padovan, Fabrizio Vincenzi, Martina Targa, Francesco Trotta, Marcello Govoni, Pier Andrea Borea

Published in: Arthritis Research & Therapy | Issue 6/2011

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Abstract

Introduction

The reduction of the inflammatory status represents one of the most important targets in rheumatoid arthritis (RA). A central role of A2A and A3 adenosine receptors (ARs) in mechanisms of inflammation has been reported in different pathologies. The primary aim of this study was to investigate the A2A and A3ARs 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 A2A and A3AR agonists in nuclear factor kB (NF-kB) pathway was evaluated. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) release was carried out by A2A and A3AR 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, A2A and A3ARs were up-regulated if compared with healthy controls. A2A and A3AR activation inhibited the NF-kB pathway and diminished inflammatory cytokines such as TNF-α, IL-1β and IL-6. A2A and A3AR agonists mediated a reduction of MMP-1 and MMP-3 release. A2A and A3AR 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 A2A and A3ARs and support the use of A2A and/or A3AR agonists as novel and effective pharmacological treatment in RA patients.
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Metadata
Title
A2A and A3 adenosine receptor expression in rheumatoid arthritis: upregulation, inverse correlation with disease activity score and suppression of inflammatory cytokine and metalloproteinase release
Authors
Katia Varani
Melissa Padovan
Fabrizio Vincenzi
Martina Targa
Francesco Trotta
Marcello Govoni
Pier Andrea Borea
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 6/2011
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar3527

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