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Disruptions in endocytic traffic contribute to the activation of the NLRP3 inflammasome.
Lee, Bali; Hoyle, Christopher; Wellens, Rose; Green, Jack P; Martin-Sanchez, Fatima; Williams, Daniel M; Matchett, Billie J; Seoane, Paula I; Bennett, Hayley; Adamson, Antony; Lopez-Castejon, Gloria; Lowe, Martin; Brough, David.
Afiliación
  • Lee B; Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UK.
  • Hoyle C; Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Group, University of Manchester, Manchester M13 9PT, UK.
  • Wellens R; Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester M13 9PT, UK.
  • Green JP; Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UK.
  • Martin-Sanchez F; Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Group, University of Manchester, Manchester M13 9PT, UK.
  • Williams DM; Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester M13 9PT, UK.
  • Matchett BJ; Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UK.
  • Seoane PI; Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Group, University of Manchester, Manchester M13 9PT, UK.
  • Bennett H; Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester M13 9PT, UK.
  • Adamson A; Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UK.
  • Lopez-Castejon G; Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Group, University of Manchester, Manchester M13 9PT, UK.
  • Lowe M; Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester M13 9PT, UK.
  • Brough D; Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester M13 9PT, UK.
Sci Signal ; 16(773): eabm7134, 2023 02 21.
Article en En | MEDLINE | ID: mdl-36809026
Inflammation driven by the NLRP3 inflammasome is coordinated through multiple signaling pathways and is regulated by subcellular organelles. Here, we tested the hypothesis that NLRP3 senses disrupted endosome trafficking to trigger inflammasome formation and inflammatory cytokine secretion. NLRP3-activating stimuli disrupted endosome trafficking and triggered localization of NLRP3 to vesicles positive for endolysosomal markers and for the inositol lipid PI4P. Chemical disruption of endosome trafficking sensitized macrophages to the NLRP3 activator imiquimod, driving enhanced inflammasome activation and cytokine secretion. Together, these data suggest that NLRP3 can sense disruptions in the trafficking of endosomal cargoes, which may explain in part the spatial activation of the NLRP3 inflammasome. These data highlight mechanisms that could be exploited in the therapeutic targeting of NLRP3.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inflamasomas / Proteína con Dominio Pirina 3 de la Familia NLR Idioma: En Revista: Sci Signal Asunto de la revista: CIENCIA / FISIOLOGIA Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inflamasomas / Proteína con Dominio Pirina 3 de la Familia NLR Idioma: En Revista: Sci Signal Asunto de la revista: CIENCIA / FISIOLOGIA Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos