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10.1038/cdd.2015.176
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Título: | Inflammasome-dependent IL-1β release depends upon membrane permeabilisation |
Otros títulos: | IL-1β release via membrane permeabilisation |
Fecha de publicación: | 2016 |
Editorial: | Nature |
Cita bibliográfica: | Cell Death & Differentiation, volumen 23, nº 7, año 2016, páginas: 1219-1231. |
ISSN: | 1476-5403 1350-9047 |
Materias relacionadas: | CDU::6 - Ciencias aplicadas |
Palabras clave: | Citocinas Macrófagos Inflamación Inflammasoma |
Resumen: | Interleukin (IL)-1β is a critical regulator of the inflammatory response. IL-1β is not secreted through the conventional ER-Golgi route of protein secretion and to-date its mechanism of release has been unknown. Crucially its secretion depends upon the processing of a precursor form following the activation of the multi-molecular inflammasome complex. Using a novel and reversible pharmacological inhibitor of the IL-1β release process, in combination with biochemical, biophysical and real-time single-cell confocal microscopy with macrophage cells expressing Venus labelled IL-1β, we have discovered that the secretion of IL-1β after inflammasome activation requires membrane permeabilisation, and occurs in parallel with the death of the secreting cell. Thus in macrophages the release of IL-1β in response to inflammasome activation appears to be a secretory process independent of non-specific leakage of proteins during cell death. The mechanism of membrane permeabilisation leading to IL-1β release is distinct from the unconventional secretory mechanism employed by its structural homologues FGF2 or IL-1α, a process that involves the formation of membrane pores but does not result in cell death. These discoveries reveal key processes at the initiation of an inflammatory response and deliver new insights into mechanisms of protein release. |
Autor/es principal/es: | Martín-Sáncez, Fátima Diamon, Catherine Zeitler, Marcel Gomez-Sanchez, Ana Baroja-Mazo, Alberto Bagnall, James Spiller, David White, Michael Daniels, Michael J. D. Mortellaro, Alessandra Peñalver, Marcos Paszek, Pawel Steringer, Julia P. Nickel, Walter Brough, David Pelegrin Vivancos, Pablo |
Facultad/Departamentos/Servicios: | Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Bioquímica y Biología Molecular B e Inmunología |
Versión del editor: | https://www.nature.com/articles/cdd2015176 |
URI: | http://hdl.handle.net/10201/137761 |
DOI: | 10.1038/cdd.2015.176 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 48 |
Derechos: | info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional |
Descripción: | ©2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted version of a Published Work that appeared in final form in Cell Death & Differentiation,. To access the final edited and published work see https://doi.org/10.1038/cdd.2015.176 |
Aparece en las colecciones: | Artículos: Bioquímica y Biología Molecular "B" e Inmunología |
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Fichero | Descripción | Tamaño | Formato | |
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2016 CDD.pdf | Versión aceptada del artículo | 5,02 MB | Adobe PDF | Visualizar/Abrir |
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