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 Szabo

Research output: Contribution to journalArticle

368 Citations (Scopus)

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 - 2000
Externally publishedYes

Fingerprint

Adenosine A2A Receptors
interleukin-12
adenosine
Interleukin-12
Adenosine
receptors
Interleukin-10
interleukin-10
Interleukin-12 Subunit p35
Purinergic P1 Receptor Agonists
Purinergic P1 Receptor Antagonists
Purine Nucleosides
Messenger RNA
Phosphorylation
Purinergic P1 Receptors
dipyridamole
Dipyridamole
Macrophages
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinases

Keywords

  • Cytokines
  • Inflammation
  • Inflammatory mediators
  • T lymphocytes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Haskó, G., Kuhel, D. G., Chen, J. F., Schwarzschild, M. A., Deitch, E. A., Mabley, J. G., ... Szabo, 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.

Adenosine inhibits IL-12 and TNF-α production via adenosine A(2a) receptor-dependent and independent mechanism. / Haskó, György; Kuhel, David G.; Chen, Jiang Fan; Schwarzschild, Michael A.; Deitch, Edwin A.; Mabley, Jon G.; Marton, Anita; Szabo, Csaba.

In: FASEB Journal, Vol. 14, No. 13, 2000, p. 2065-2074.

Research output: Contribution to journalArticle

Haskó, G, Kuhel, DG, Chen, JF, Schwarzschild, MA, Deitch, EA, Mabley, JG, Marton, A & Szabo, C 2000, 'Adenosine inhibits IL-12 and TNF-α production via adenosine A(2a) receptor-dependent and independent mechanism', FASEB Journal, vol. 14, no. 13, pp. 2065-2074.
Haskó G, Kuhel DG, Chen JF, Schwarzschild MA, Deitch EA, Mabley JG et al. Adenosine inhibits IL-12 and TNF-α production via adenosine A(2a) receptor-dependent and independent mechanism. FASEB Journal. 2000;14(13):2065-2074.
Haskó, György ; Kuhel, David G. ; Chen, Jiang Fan ; Schwarzschild, Michael A. ; Deitch, Edwin A. ; Mabley, Jon G. ; Marton, Anita ; Szabo, Csaba. / Adenosine inhibits IL-12 and TNF-α production via adenosine A(2a) receptor-dependent and independent mechanism. In: FASEB Journal. 2000 ; Vol. 14, No. 13. pp. 2065-2074.
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