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Xanthine oxidoreductase regulates macrophage IL1ß secretion upon NLRP3 inflammasome activation.
Ives, Annette; Nomura, Johji; Martinon, Fabio; Roger, Thierry; LeRoy, Didier; Miner, Jeffrey N; Simon, Gregoire; Busso, Nathalie; So, Alexander.
Afiliación
  • Ives A; Rheumatology Laboratory, Centre Hospitalier Universitaire Vaudois, Ave Pierre Decker 4, 1011 Lausanne, Switzerland.
  • Nomura J; 1] Rheumatology Laboratory, Centre Hospitalier Universitaire Vaudois, Ave Pierre Decker 4, 1011 Lausanne, Switzerland [2] Pharmaceutical Development Research Laboratories, Teijin Institute for Bio-Medical Research, Teijin Pharma Limited, Hino, 1918512 Tokyo, Japan.
  • Martinon F; Department of Biochemistry, University of Lausanne, chemin des Boveresses 155, 1066 Epalinges, Switzerland.
  • Roger T; Infectious Diseases laboratory, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.
  • LeRoy D; Infectious Diseases laboratory, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.
  • Miner JN; Ardea Biosciences, San Diego, 92121 California, USA.
  • Simon G; Rheumatology Laboratory, Centre Hospitalier Universitaire Vaudois, Ave Pierre Decker 4, 1011 Lausanne, Switzerland.
  • Busso N; Rheumatology Laboratory, Centre Hospitalier Universitaire Vaudois, Ave Pierre Decker 4, 1011 Lausanne, Switzerland.
  • So A; Rheumatology Laboratory, Centre Hospitalier Universitaire Vaudois, Ave Pierre Decker 4, 1011 Lausanne, Switzerland.
Nat Commun ; 6: 6555, 2015 Mar 24.
Article en En | MEDLINE | ID: mdl-25800347
Activation of the NLRP3 inflammasome by microbial ligands or tissue damage requires intracellular generation of reactive oxygen species (ROS). We present evidence that macrophage secretion of IL1ß upon stimulation with ATP, crystals or LPS is mediated by a rapid increase in the activity of xanthine oxidase (XO), the oxidized form of xanthine dehydrogenase, resulting in the formation of uric acid as well as ROS. We show that XO-derived ROS, but not uric acid, is the trigger for IL1ß release and that XO blockade results in impaired IL1ß and caspase1 secretion. XO is localized to both cytoplasmic and mitochondrial compartments and acts upstream to the PI3K-AKT signalling pathway that results in mitochondrial ROS generation. This pathway represents a mechanism for regulating NLRP3 inflammasome activation that may have therapeutic implications in inflammatory diseases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Xantina Deshidrogenasa / Xantina Oxidasa / Proteínas Portadoras / Especies Reactivas de Oxígeno / Interleucina-1beta / Macrófagos Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2015 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Xantina Deshidrogenasa / Xantina Oxidasa / Proteínas Portadoras / Especies Reactivas de Oxígeno / Interleucina-1beta / Macrófagos Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2015 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Reino Unido