Adenosine inhibits IL-12 and TNF-α production via adenosine A(2a) receptor-dependent and independent mechanism

György Haskó, David G. Kuhel, Jiang Fan Chen, Michael A. Schwarzschild, Edwin A. Deitch, Jon G. Mabley, Anita Marton, Csaba Szabó

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    375 Scopus citations

    Abstract

    Interleukin 12 (IL-12) is a crucial cytokine in the regulation of T helper 1 vs. T helper 2 immune responses. In the present study, we investigated the effect of the endogenous purine nucleoside adenosine on the production of IL-12. In mouse macrophages, adenosine suppressed IL-12 production. Although the order of potency of adenosine receptor agonists suggested the involvement of A(2a) receptors, data obtained with A(2a) receptor-deficient mice showed that the adenosine suppression of IL-12 and even TNF-α production is only partly mediated by A(2a) receptor ligation. Studies with adenosine receptor antagonists or the adenosine uptake blocker dipyridamole showed that adenosine released endogenously also decreases IL-12. Although adenosine increases IL-10 production, the inhibition of IL-12 production is independent of the increased IL-10. The mechanism of action of adenosine was not associated with alterations of the activation of the p38 and p42/p44 mitogen-activated protein kinases or the phosphorylation of the c-Jun terminal kinase. Adenosine failed to affect steady-state levels of either IL-12 p35 or p40 mRNA, but augmented IL-10 mRNA levels. In summary, adenosine inhibits IL-12 production via various adenosine receptors. These results support the notion that adenosine-based therapies might be useful in certain autoimmune and/or inflammatory diseases.

    Original languageEnglish (US)
    Pages (from-to)2065-2074
    Number of pages10
    JournalFASEB Journal
    Volume14
    Issue number13
    StatePublished - Oct 16 2000

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    Keywords

    • Cytokines
    • Inflammation
    • Inflammatory mediators
    • T lymphocytes

    ASJC Scopus subject areas

    • Biotechnology
    • Biochemistry
    • Molecular Biology
    • Genetics

    Cite this

    Haskó, G., Kuhel, D. G., Chen, J. F., Schwarzschild, M. A., Deitch, E. A., Mabley, J. G., Marton, A., & Szabó, C. (2000). Adenosine inhibits IL-12 and TNF-α production via adenosine A(2a) receptor-dependent and independent mechanism. FASEB Journal, 14(13), 2065-2074.