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10.4049/jimmunol.180.11.7147
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Título: | P2X7 receptor differentially couples to distinct release pathways for IL-1b in mouse macrophage |
Fecha de publicación: | 2008 |
Editorial: | The American Association of Immunologists, Inc. |
Cita bibliográfica: | The Journal of Immunology, volumen 180, nº 11, año 2008, páginas 7147-7157 |
Materias relacionadas: | CDU::6 - Ciencias aplicadas |
Palabras clave: | Ratones Macrófagos Citocinas LPS Inflamación |
Resumen: | The pro-inflammatory IL-1 cytokines, IL-1a, IL-1b and IL-18, are key mediators of the acute immune response to injury and infection. Mechanisms underlying their cellular release remain unclear. Activation of purinergic P2X7 receptors (P2X7R) by extracellular ATP is a key physiological inducer of rapid IL-1brelease from LPS-primed macrophage. We investigated patterns of ATP-mediated release of IL-1 cytokines from three macrophage types in attempts to provide direct evidence for or against distinct release mechanisms. We used peritoneal macrophage from P2X7R-/- mice and found that release of IL-1a, IL-18, as well as IL-1b, by ATP resulted exclusively from activation of P2X7R, that release of all these IL-1 cytokines involved pannexin-1 (panx1), and that there was both a panx1-dependent and independent component to IL-1b release. We compared IL-1 release patterns from LPS-primed peritoneal macrophage, RAW264.7 macrophage and J774A.1 macrophage. We found RAW264.7 macrophage readily release pro-IL- 1b independently of panx1 but do not release mature IL-1b because they do not express apoptotic speck-like protein with a caspase-activating recruiting domain (ASC) and so have no caspase-1 inflammasome activity. We delineated two distinct release pathways: the well-known caspase-1 cascade mediating release of processed IL-1b that was selectively blocked by inhibition of caspase-1 or panx1, and a calcium-independent, caspase-1/panx1-independent release of pro-IL-1b that was selectively blocked by glycine. None of these release responses were associated with cell damage or cytolytic effects. This provides the first direct demonstration of a distinct signaling mechanism responsible for ATP-induced release of pro-IL-1b. |
Autor/es principal/es: | Pelegrin, Pablo Barroso-Gutierrez, Consuelo Surprenant, Annmarie |
Facultad/Departamentos/Servicios: | Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Bioquímica y Biología Molecular B e Inmunología |
Versión del editor: | https://journals.aai.org/jimmunol/article/180/11/7147/84652/P2X7-Receptor-Differentially-Couples-to-Distinct |
URI: | http://hdl.handle.net/10201/137734 |
DOI: | 10.4049/jimmunol.180.11.7147 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 39 |
Derechos: | info:eu-repo/semantics/embargoedAccess |
Aparece en las colecciones: | Artículos: Bioquímica y Biología Molecular "B" e Inmunología |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
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2008 JI.pdf | Versión aceptada del artículo | 3,86 MB | Adobe PDF | Visualizar/Abrir Solicitar una copia |
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