Interleukin-10 expression in lipopolysaccharide-activated microglia is mediated by extracellular ATP in an autocrine fashion.

Abstract

Immune cells have been shown to release ATP into the extracellular space to provide auto- and paracrine purinergic modulation of immune and inflammatory responses. In the present study, we demonstrate that ATP released from lipopolysaccharide (LPS)-stimulated microglia induces interleukin-10 (IL-10) expression in an autocrine manner. The expression as well as secretion of IL-10 by LPS-stimulated microglia was completely inhibited by apyrase, ATP-hydrolyzing enzyme, whereas tumor necrosis factor-alpha (TNF-alpha) expression was unaffected. LPS-activated microglia rapidly released a low concentration of ATP (10-20 nM) into the medium, and the nanomolar range of extracellular ATP, ADP, adenosine 5'-O-(3-thiotriphosphate) (ATP-gamma-S), and adenosine 5'-O-(2-thiodiphosphate) (ADP-beta-S) induced IL-10 secretion from microglia in a dose-dependent manner. These results suggest that ATP released from LPS-activated microglia and/or a metabolite of ATP (ADP) may induce IL-10 expression through P2Y purinergic receptors.