title: Multiple sclerosis lymphocytes upregulate A2A adenosine receptors that are antiinflammatory when stimulated.
abstract: 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 A2A ARs in the inhibition of key pro-inflammatory mediators for the pathogenesis of MS. In lymphocytes from MS patients, A1, A2A, A2B, and A3 ARs were analyzed by using RT-PCR, Western blotting, immunofluorescence, and binding assays. Moreover the effect of A2A AR 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 A2A AR agonist on the modulation of very late antigen (VLA)-4 expression and NF-κB was also explored. A2A 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-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 A2A AR agonists could represent a novel therapeutic tool for MS treatment as suggested by the antiinflammatory role of A2A ARs in lymphocytes from MS patients.
authors: Department of Medical Sciences, Pharmacology Section, University of Ferrara, Ferrara, Italy.
authors: Fabrizio
authors: F
authors: Vincenzi
authors: Carmen
authors: C
authors: Corciulo
authors: Martina
authors: M
authors: Targa
authors: Stefania
authors: S
authors: Merighi
authors: Stefania
authors: S
authors: Gessi
authors: Ilaria
authors: I
authors: Casetta
authors: Mauro
authors: M
authors: Gentile
authors: Enrico
authors: E
authors: Granieri
authors: Pier Andrea
authors: PA
authors: Borea
authors: Katia
authors: K
authors: Varani
mesh_terms: D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology*; D000328:Adult; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D039041:Integrin alpha4beta1 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D009103:Multiple Sclerosis / Q000276:immunology*; D016328:NF-kappa B / Q000096:biosynthesis; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D058908:Adenosine A2 Receptor Agonists; D039041:Integrin alpha4beta1; D020381:Interleukin-17; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D043705:Receptor, Adenosine A2A; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: A2A adenosine receptors; Human lymphocytes; Multiple sclerosis; Proinflammatory cytokines; Very late antigen 4 (VLA-4)