Pharmacological preconditioning with adenosine A1 receptor agonist suppresses cellular immune response by an A2A receptor dependent mechanism

Oshri Naamani, Cidio Chaimovitz, Amos Douvdevani

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Under stressful conditions such as ischemia, sepsis, and severe trauma, adenosine levels are elevated and protect the tissue by interaction with G coupled receptors. In a model of peritonitis, we previously found that pharmacological preconditioning (PPC) of mice with a selective adenosine A 1 receptor (A1R) agonist, 2-chloro-N(6)- cyclopentyladenosine (CCPA), induced the A2AR which reduces cytokine secretion and leukocyte recruitment. In our present study we determined whether mice PPC will moderate cellular immune response by the same mechanism. Similar to the effect on inflammation, PPC reduced the response to lymphocyte mitogens and allogeneic MLR response. The inhibitory effect of PPC on the immune response was A1R and A2AR dependent as illustrated by experiments with antagonists of these receptors and mice with knock down (KO) receptors. In MLR with PPC splenocytes we found reduced levels of pro-inflammatory cytokines (IFN-γ, IL-15, TNF-α) and elevation of IL-10, as well as elevation of regulatory T-cell. Our data indicate that PPC is able to remarkably suppress cellular immune response due to the sensitization A2AR. This effect of PPC sheds light on the protective role of adenosine in ischemic preconditioning and makes this treatment candidate for the prevention of graft rejection.

Original languageEnglish
Pages (from-to)205-212
Number of pages8
JournalInternational Immunopharmacology
Volume20
Issue number1
DOIs
StatePublished - 1 Jan 2014

Keywords

  • Cellular activation
  • Cytokines
  • MLR
  • Regulatory T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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