Multiple sclerosis lymphocytes upregulate A(2A) adenosine receptors that are antiinflammatory when stimulated

Multiple sclerosis (MS) is an autoimmune-mediated inflammatory disease characterized by multifocal areas of demyelination. Experimental evidence indicates that A2A adenosine receptors (ARs) play a pivotal role in the inhibition of inflammatory processes. The aim of this study was to investigate the contribution of A2AARs in the inhibition of key pro-inflammatory mediators for the pathogenesis of MS. In lymphocytes from MS patients, A1, A2A, A2B, and A3ARs were analyzed by using RT-PCR, Western blotting, immunofluorescence, and binding assays. Moreover the effect of A2AAR stimulation on proinflammatory cytokine release such as TNF-α, IFN-γ, IL-6, IL-1β, IL-17, and on lymphocyte proliferation was evaluated. The capability of an A2AAR agonist on the modulation of very late antigen (VLA)-4 expression and NF-κB was also explored. A2AAR upregulation was observed in lymphocytes from MS patients in comparison with healthy subjects. The stimulation of these receptors mediated a significant inhibition of TNF-α, IFN-γ, IL-6, IL-1β, IL-17, and cell proliferation as well as VLA-4 expression and NF-κB activation. This new evidence highlights that A2AAR agonists could represent a novel therapeutic tool for MS treatment as suggested by the antiinflammatory role of A2AARs in lymphocytes from MS patients. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.