Original Article

Purinergic Signalling

, Volume 9, Issue 3, pp 325-336

First online:

Anti-inflammatory effects of inosine in allergic lung inflammation in mice: evidence for the participation of adenosine A2A and A3 receptors

  • Fernanda da Rocha LapaAffiliated withDepartment of Pharmacology, Center of Biological Sciences, Federal University of ParanáDepartment of Pharmacology, Center of Biological Sciences, Federal University of Santa Catarina
  • , Ana Paula Ligeiro de OliveiraAffiliated withDepartment of Health Sciences, Universidade Nove de Julho
  • , Beatriz Golega AccetturiAffiliated withDepartment of Pharmacology, Biomedical Sciences Institute, University of São Paulo
  • , Isabelli de Oliveira MartinsAffiliated withDepartment of Pharmacology, Biomedical Sciences Institute, University of São Paulo
  • , Helory Vanni DomingosAffiliated withDepartment of Pharmacology, Biomedical Sciences Institute, University of São Paulo
  • , Daniela de Almeida CabriniAffiliated withDepartment of Pharmacology, Center of Biological Sciences, Federal University of Paraná
  • , Wothan Tavares de LimaAffiliated withDepartment of Pharmacology, Biomedical Sciences Institute, University of São Paulo
  • , Adair Roberto Soares SantosAffiliated withDepartment of Physiological Sciences, Federal University of Santa Catarina Email author 

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Abstract

Inosine, a naturally occurring purine formed from the breakdown of adenosine, is associated with immunoregulatory effects. Evidence shows that inosine modulates lung inflammation and regulates cytokine generation. However, its role in controlling allergen-induced lung inflammation has yet to be identified. In this study, we aimed to investigate the role of inosine and adenosine receptors in a murine model of lung allergy induced by ovalbumin (OVA). Intraperitoneal administration of inosine (0.001–10 mg/kg, 30 min before OVA challenge) significantly reduced the number of leukocytes, macrophages, lymphocytes and eosinophils recovered in the bronchoalveolar lavage fluid of sensitized mice compared with controls. Interestingly, our results showed that pre-treatment with the selective A2A receptor antagonist (ZM241385), but not with the selective A2B receptor antagonist (alloxazine), reduced the inhibitory effects of inosine against macrophage count, suggesting that A2A receptors mediate monocyte recruitment into the lungs. In addition, the pre-treatment of mice with selective A3 antagonist (MRS3777) also prevented inosine effects against macrophages, lymphocytes and eosinophils. Histological analysis confirmed the effects of inosine and A2A adenosine receptors on cell recruitment and demonstrated that the treatment with ZM241385 and alloxazine reverted inosine effects against mast cell migration into the lungs. Accordingly, the treatment with inosine reduced lung elastance, an effect related to A2 receptors. Moreover, inosine reduced the levels of Th2-cytokines, interleukin-4 and interleukin-5, an effect that was not reversed by A2A or A2B selective antagonists. Our data show that inosine acting on A2A or A3 adenosine receptors can regulate OVA-induced allergic lung inflammation and also implicate inosine as an endogenous modulator of inflammatory processes observed in the lungs of asthmatic patients.

Keywords

Inosine Adenosine receptors Allergy Ovalbumin