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.