MLKL Activation Triggers NLRP3-Mediated Processing and Release of IL-1ß Independently of Gasdermin-D.
J Immunol
; 198(5): 2156-2164, 2017 03 01.
Article
en En
| MEDLINE
| ID: mdl-28130493
ABSTRACT
Necroptosis is a form of programmed cell death defined by activation of the kinase receptor interacting protein kinase 3 and its downstream effector, the pseudokinase mixed lineage kinase domain-like (MLKL). Activated MLKL translocates to the cell membrane and disrupts it, leading to loss of cellular ion homeostasis. In this study, we use a system in which this event can be specifically triggered by a small-molecule ligand to show that MLKL activation is sufficient to induce the processing and release of bioactive IL-1ß. MLKL activation triggers potassium efflux and assembly of the NLRP3 inflammasome, which is required for the processing and activity of IL-1ß released during necroptosis. Notably, MLKL activation also causes cell membrane disruption, which allows efficient release of IL-1ß independently of the recently described pyroptotic effector gasdermin-D. Taken together, our findings indicate that MLKL is an endogenous activator of the NLRP3 inflammasome, and that MLKL activation provides a mechanism for concurrent processing and release of IL-1ß independently of gasdermin-D.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Quinasas
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Monocitos
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Apoptosis
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Interleucina-1beta
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Inflamasomas
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Proteína con Dominio Pirina 3 de la Familia NLR
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Necrosis
Límite:
Humans
Idioma:
En
Año:
2017
Tipo del documento:
Article