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.
- Human peripheral blood mononuclear cells
- Intercellular adhesion molecule-1
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