Multiple sclerosis lymphocytes upregulate A2A 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 A(2A) adenosine receptors (ARs) play a pivotal role in the inhibition of inflammatory processes. The aim of this study was to investigate the contribution of A(2A)ARs in the inhibition of key pro-inflammatory mediators for the pathogenesis of MS. In lymphocytes from MS patients, A(1), A(2A), A(2B), and A(3)ARs were analyzed by using RT-PCR, Western blotting, immunofluorescence, and binding assays. Moreover the effect of A(2A)AR stimulation on proinflammatory cytokine release such as TNF-, IFN-, IL-6, IL-1, IL-17, and on lymphocyte proliferation was evaluated. The capability of an A(2A)AR agonist on the modulation of very late antigen (VLA)-4 expression and NF-B was also explored. A(2A)AR upregulation was observed in lymphocytes from MS patients in comparison with healthy subjects. The stimulation of these receptors mediated a significant inhibition of TNF-, IFN-, IL-6, IL-1, IL-17, and cell proliferation as well as VLA-4 expression and NF-B activation. This new evidence highlights that A(2A)AR agonists could represent a novel therapeutic tool for MS treatment as suggested by the antiinflammatory role of A(2A)ARs in lymphocytes from MS patients.