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

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Abstract

Background and purpose:

Adenosine suppresses immune responses through adenosine2A (A2A) 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 assay.

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 A2A receptor antagonist reversed the action of adenosine, an A1 or A3 receptor antagonist enhanced them. An A2A receptor agonist, CGS21680, mimicked the effects of adenosine and its effects were abolished not only by the A2A receptor antagonist but also by A1 or A3 receptor agonists. Activation via A2A receptors resulted in elevation of cAMP in monocytes, whereas the stimulation of A1 or A3 receptors inhibited it, suggesting that intracellular signal transduction following ligation of A2A receptors might be blocked by activation of A1 or A3 receptors.

Conclusions and Implications:

Adenosine differentially regulates IL-18-induced adhesion molecule expression and cytokine production through several subtypes of its receptors.

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