title: A2A adenosine receptor upregulation correlates with disease activity in patients with systemic lupus erythematosus.
abstract: Adenosine is a purine nucleoside implicated in the regulation of the innate and adaptive immune systems, acting through its interaction with four cell surface receptors: A1, A2A, A2B, and A3. There is intense interest in understanding how adenosine functions in health and during disease, but surprisingly little is known about the actual role of adenosine-mediated mechanisms in systemic lupus erythematosus (SLE). With this background, the aim of the present study was to test the hypothesis that dysregulation of A1, A2A, A2B, and A3 adenosine receptors (ARs) in lymphocytes of patients with SLE may be involved in the pathogenesis of the disease and to examine the correlations between the status of the ARs and the clinical parameters of SLE.
  
  
  
  ARs were analyzed by performing saturation-binding assays, as well as messenger RNA and Western blot analysis, with lymphocytes of patients with SLE in comparison with healthy subjects. We tested the effect of A2AAR agonists in the nuclear factor kB (NF-kB) pathway and on the release of interferon (IFN)-α; tumor necrosis factor (TNF)-α; and interleukin (IL)-2, IL-6, IL-1β, and IL-10.
  
  
  
  In lymphocytes obtained from 80 patients with SLE, A2AARs were upregulated compared with those of 80 age-matched healthy control subjects, while A1, A2B, and A3 ARs were unchanged. A2AAR density was inversely correlated with Systemic Lupus Erythematosus Disease Activity Index 2000 score disease activity through time evaluated according to disease course patterns, serositis, hypocomplementemia, and anti-double-stranded DNA positivity. A2AAR activation inhibited the NF-kB activation pathway and diminished inflammatory cytokines (IFN-α, TNF-α, IL-2, IL-6, IL-1β), but it potentiated the release of anti-inflammatory IL-10.
  
  
  
  These data suggest the involvement of A2AARs in the complex pathogenetic network of SLE, acting as a modulator of the inflammatory process. It could represent a compensatory pathway to better counteract disease activity. A2AAR activation significantly reduced the release of proinflammatory cytokines while enhancing those with anti-inflammatory activity, suggesting a potential translational use of A2AAR agonists in SLE pharmacological treatment.
authors: Department of Medical Science, Section of Rheumatology, University of Ferrara, Ferrara and Azienda Ospedaliero-Universitaria Sant'Anna di Ferrara, Ferrara Cona (Ferrara) Via Aldo Moro 8 44124 Cona, Ferrara, Italy. brtlsn1@unife.it.
authors: Alessandra
authors: 0000-0003-2416-8134
authors: A
authors: Bortoluzzi
authors: Department of Medical Sciences, Institute of Pharmacology, University of Ferrara, Via Fossato di Mortara 17-19, Ferrara, Italy.
authors: Fabrizio
authors: F
authors: Vincenzi
authors: Department of Medical Science, Section of Rheumatology, University of Ferrara, Ferrara and Azienda Ospedaliero-Universitaria Sant'Anna di Ferrara, Ferrara Cona (Ferrara) Via Aldo Moro 8 44124 Cona, Ferrara, Italy.
authors: Marcello
authors: M
authors: Govoni
authors: Department of Medical Science, Section of Rheumatology, University of Ferrara, Ferrara and Azienda Ospedaliero-Universitaria Sant'Anna di Ferrara, Ferrara Cona (Ferrara) Via Aldo Moro 8 44124 Cona, Ferrara, Italy.
authors: Melissa
authors: M
authors: Padovan
authors: Department of Medical Sciences, Institute of Pharmacology, University of Ferrara, Via Fossato di Mortara 17-19, Ferrara, Italy.
authors: Annalisa
authors: A
authors: Ravani
authors: Department of Medical Sciences, Institute of Pharmacology, University of Ferrara, Via Fossato di Mortara 17-19, Ferrara, Italy.
authors: Pier Andrea
authors: PA
authors: Borea
authors: Department of Medical Sciences, Institute of Pharmacology, University of Ferrara, Via Fossato di Mortara 17-19, Ferrara, Italy.
authors: Katia
authors: K
authors: Varani
mesh_terms: D000328:Adult; D015153:Blotting, Western; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D043705:Receptor, Adenosine A2A / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D043705:Receptor, Adenosine A2A
keywords: A2A adenosine receptor; Disease activity; Systemic lupus erythematosus