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Effects of adenosine on adhesion molecule expression and cytokine production in human PBMC depend on the receptor subtype activated
Author(s) -
Takahashi H K,
Iwagaki H,
Hamano R,
Wake H,
Kanke T,
Liu K,
Yoshino T,
Tanaka N,
Nishibori M
Publication year - 2007
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0707126
Subject(s) - adenosine , adenosine a3 receptor , adenosine receptor , adenosine a2b receptor , receptor , cytokine , purinergic signalling , agonist , adenosine a1 receptor , tumor necrosis factor alpha , receptor antagonist , intercellular adhesion molecule 1 , biology , receptor expression , chemistry , endocrinology , microbiology and biotechnology , medicine , cell adhesion molecule , immunology , biochemistry , antagonist
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 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 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. British Journal of Pharmacology (2007) 150 , 816–822. doi: 10.1038/sj.bjp.0707126