Interleukin-10 expression in lipopolysaccharide-activated microglia is mediated by extracellular ATP in an autocrine fashion.
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.
Seo
Dong Reoyl
DR
Brain Disease Research Center, Ajou University School of Medicine, San-5 Wonchon-dong, Youngtong-gu, Suwon, Korea 443-721.
Kim
Kyung You
KY
Lee
Yong Beom
YB
D000255:Adenosine Triphosphate / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D008070:Lipopolysaccharides; D016753:Interleukin-10; D000255:Adenosine Triphosphate