A Key Role for Redox Signaling in Rapid P2X7 Receptor-Induced IL-1β Processing in Human Monocytes

• DOI: 10.4049/jimmunol.180.12.8410
• Publication Date: 2014-04-18T23:24:59Z
• Authors: James Hewinson; Samantha F Moore; Christian Glover; Andrew G Watts; Amanda B MacKenzie
• Keywords: Interleukin-1beta; 610; NADPH Oxidase; Nitric Oxide; Monocytes; Cell Line; 03 medical and health sciences; Adenosine Triphosphate; Cell Line, Tumor; Receptors; Humans; Protein Processing; 0303 health sciences; Purinergic P2; Tumor; S-Nitrosothiols; Receptors, Purinergic P2; Caspase 1; Post-Translational; NADPH Oxidases; Extracellular Fluid; Oxidants; Enzyme Activation; Receptors, Purinergic P2X7; Purinergic P2X7; Ion Channel Gating; Oxidation-Reduction; Protein Processing, Post-Translational; Signal Transduction

Abstract P2X7 receptors (P2X7Rs) are ATP-gated ion channels that trigger caspase-1 activation in the presence of TLR ligands. Inflammatory is responsible for proteolytic IL-1β. However, signaling events couple P2X7Rs to remain undefined. In this study we demonstrate ATP-induced cellular oxidation critical and subsequent IL-1β processing. Purinergic receptor stimulation, including P2X7Rs, endotoxin-primed human monocytes augments NADPH oxidase activity whereas concurrent purinergic stimulation triggers protein denitroyslation, leading formation peroxynitrite. cleavage blocked under conditions where superoxide anion or treated with antioxidants a peroxynitrite scavenger. Nigericin, K+/H+ antiporter, also increases activity, processing by scavenger inhibition oxidase. These data via fundamental mature induced P2X7R stimulation.