Purinergic (P2X7) receptor activation of microglia induces cell death via an interleukin-1-independent mechanism.
Activation of purinergic P2X7 receptors, principally by extracellular ATP, promotes the processing and release of the cytokine interleukin-1beta (IL-1beta) and induces cell death in activated microglia and macrophages. The objective of this study was to determine if IL-1beta release contributes directly to this cell death in microglia. Exposure of microglia to bacterial lipopolysaccharide (LPS) and ATP induced release of IL-1beta and IL-1alpha, as well as cell death. Neither cell death nor IL-1 release was observed in microglia lacking the P2X7 receptor. Microglia from mice lacking the IL-1beta gene demonstrated a profile of death identical to that of wild-type microglia in response to LPS and ATP. Thus, IL-1beta is not required for P2X7 receptor-stimulated microglial death.
Brough
David
D
Division of Neuroscience, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
Le Feuvre
Rosalind A
RA
Iwakura
Yoichiro
Y
Rothwell
Nancy J
NJ
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004347:Drug Interactions / Q000502:physiology; D004660:Encephalitis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005911:Gliosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007375:Interleukin-1 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7
D007375:Interleukin-1; D008070:Lipopolysaccharides; C546469:P2rx7 protein, mouse; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate