Adenosine receptor agonists inhibit Macrophage Inflammatory Protein (MIP)-1α production in immunostimulated macrophages

Ligands of the various adenosine receptor subtypes have been shown to modulate the production of pro-and anti-inflammatory cytokines. Macrophage inflammatory protein (MP) 1α is a chemokine which enhances neutrophil recruitment into inflammatory sites. Here we evaluated the effect of various ligands of the adenosine receptors on MIP-1α production in immunostimulated RAW macrophages in vitro. The A₃ receptor agonist N⁶-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (IB-MECA), and, less potently, the A₂ receptor agonist CGS-21680 (1-200 μM) dose-dependently suppressed the production of MIP-1α, whereas the selective A₁ receptor agonist 2-chloro-N6-cyclopentyladenosine was ineffective, and adenosine was a weak inhibitor. The inhibition by the adenosine agonists was associated with suppression of MIP-1α steady-state mRNA levels. These data demonstrate that activation of the A₃, and to a lesser extent A₂ adenosine receptors suppresses MIP-1α expression in immunostimulated macrophages. This effect may contribute to the immunosuppressive properties of adenosine or adenosine receptor ligands in inflammatory conditions.