Effects of Adenosine on Adhesion Molecule Expression and Cytokine Production in Human PBMC Depend on the Receptor Subtype Activated

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2007 Feb 21

PMID 17310143

Citations 15

Authors

H K Takahashi

H Iwagaki

R Hamano

H Wake

T Kanke

K Liu

T Yoshino

N Tanaka

M Nishibori

Affiliations

Soon will be listed here.

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)-gamma and tumor necrosis factor (TNF)-alpha 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-gamma and TNF-alpha by PBMC.

Experimental Approach: The expression of ICAM-1 was examined by flow cytometry. IL-12, IFN-gamma and TNF-alpha 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-gamma and TNF-alpha. 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.

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