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Anti-inflammatory effects of purine nucleosides, adenosine and inosine, in a mouse model of pleurisy: evidence for the role of adenosine A2 receptors

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Abstract

Adenosine and its metabolite, inosine, have been described as molecules that participate in regulation of inflammatory response. The aim of this study was to investigate the effect of adenosine and inosine in a mouse model of carrageenan-induced pleurisy as well as the participation of adenosine receptors in this response. Injection of carrageenan into the pleural cavity induced an acute inflammatory response characterized by leukocyte migration, pleural exudation, and increased release of interleukin-1β and tumor necrosis factor-α in pleural exudates. The treatment with adenosine (0.3–100 mg/kg, i.p.) and inosine (0.1–300 mg/kg, i.p.) 30 min before carrageenan injection reduced significantly all these parameters analyzed. Our results also demonstrated that A2A and A2B receptors seem to mediate the adenosine and inosine effects observed, since pretreatment with selective antagonists of adenosine A2A (ZM241385) and A2B (alloxazine) receptors, reverted the inhibitory effects of adenosine and inosine in pleural inflammation. The involvement of A2 receptors was reinforced with adenosine receptor agonist CGS21680 treatment, since its anti-inflammatory effects were reversed completely and partially with ZM241385 and alloxazine injection, respectively. Moreover, the combined treatment with subeffective dose of adenosine (0.3 mg/kg) and inosine (1.0 mg/kg) induced a synergistic anti-inflammatory effect. Thus, based on these findings, we propose that inosine contributes with adenosine to exert anti-inflammatory effects in pleural inflammation, reinforcing the notion that endogenous nucleosides play an important role in controlling inflammatory diseases. This effect is likely mediated by the activation of adenosine A2 subtype receptors and inhibition of production or release of pro-inflammatory cytokines.

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Acknowledgments

This work was supported by grants from Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior and Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil.

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  1. Graduate Program in Pharmacology, Department of Pharmacology, Center of Biological Sciences, Federal University of Paraná, Curitiba, 88015-420, PR, Brazil

    Fernanda da Rocha Lapa, Daniela de Almeida Cabrini & Adair R. S. Santos

  2. Laboratory of Neurobiology of Pain and Inflammation, Department of Physiological Sciences, Federal University of Santa Catarina, Trindade, 88040-900, Florianopolis, SC, Brazil

    Morgana Duarte da Silva & Adair R. S. Santos

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  1. Fernanda da Rocha Lapa
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da Rocha Lapa, F., da Silva, M.D., de Almeida Cabrini, D. et al. Anti-inflammatory effects of purine nucleosides, adenosine and inosine, in a mouse model of pleurisy: evidence for the role of adenosine A2 receptors. Purinergic Signalling 8, 693–704 (2012). https://doi.org/10.1007/s11302-012-9299-2

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