Effects of adenosine on adhesion molecule expression and cytokine production in human PBMC depend on the receptor subtype activated

H. K. Takahashi, H. Iwagaki, R. Hamano, H. Wake, T. Kanke, K. Liu, T. Yoshino, N. Tanaka, M. Nishibori

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background and purpose: Adenosine suppresses immune responses through adenosine 2A (A 2A) receptors, by raising intracellular cAMP. Interleukin (IL)-18 up-regulates the expression of intercellular adhesion molecule (ICAM)-1 on monocytes, leading to production of pro-inflammatory cytokines such as IL-12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α by human peripheral blood mononuclear cells (PBMC). We have previously demonstrated that elevation of cAMP inhibits this IL-18-induced expression of adhesion molecules. In the present study, we examined the effect of adenosine on the IL-18-induced up-regulation of ICAM-1 on human monocytes and production of IL-12, IFN-γ and TNF-α by PBMC. Experimental approach: The expression of ICAM-1 was examined by flow cytometry. IL-12, IFN-γ and TNF-α were determined by ELISA ass1ay. Key results: Adenosine inhibited the IL-18-induced up-regulation of ICAM-1 on human monocytes and it abolished the IL-18-enhanced production of IL-12, IFN-γ and TNF-α. While an A 2A receptor antagonist reversed the action of adenosine, an A 1 or A 3 receptor antagonist enhanced them. An A 2A receptor agonist, CGS21680, mimicked the effects of adenosine and its effects were abolished not only by the A 2A receptor antagonist but also by A 1 or A 3 receptor agonists. Activation via A 2A receptors resulted in elevation of cAMP in monocytes, whereas the stimulation of A 1 or A 3 receptors inhibited it, suggesting that intracellular signal transduction following ligation of A 2A receptors might be blocked by activation of A 1 or A 3 receptors. Conclusions and Implications: Adenosine differentially regulates IL-18-induced adhesion molecule expression and cytokine production through several subtypes of its receptors.

Original languageEnglish
Pages (from-to)816-822
Number of pages7
JournalBritish Journal of Pharmacology
Volume150
Issue number6
DOIs
Publication statusPublished - Mar 18 2007

Keywords

  • Adenosine
  • Cytokine
  • Human peripheral blood mononuclear cells
  • Intercellular adhesion molecule-1
  • Interleukin-18

ASJC Scopus subject areas

  • Pharmacology

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