Inhibition of IRE1α RNase activity reduces NLRP3 inflammasome assembly and processing of pro-IL1ß.
Cell Death Dis
; 10(9): 622, 2019 08 16.
Article
em En
| MEDLINE
| ID: mdl-31417078
ABSTRACT
The inflammasome is a multiprotein complex assembled in response to Pathogen Associated Molecular Patterns (PAMPs) and Danger Associated Molecular Patterns (DAMPs). Inflammasome activation occurs through a two-step mechanism, with the first signal facilitating priming of inflammasome components while the second signal triggers complex assembly. Once assembled, the inflammasome recruits and activates pro-caspase-1, which in turn processes pro-interleukin (IL)-18 and pro-IL-1ß into their bio-active forms. Owing to its key role in the regulation of innate immune responses, the inflammasome has emerged as a therapeutic target for the treatment of inflammatory conditions. In this study we demonstrate that IRE1α, a key component of the Unfolded Protein Response, contributes to assembly of the NLRP3 inflammasome. Blockade of IRE1α RNase signaling lowered NLRP3 inflammasome assembly, caspase-1 activation and pro-IL-1ß processing. These results underscore both the importance and potential therapeutic relevance of targeting IRE1α signaling in conditions of excessive inflammasome formation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Precursores de Proteínas
/
Interleucina-1
/
Proteínas Serina-Treonina Quinases
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Endorribonucleases
/
Interleucina-1beta
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Inflamassomos
/
Proteína 3 que Contém Domínio de Pirina da Família NLR
Limite:
Humans
Idioma:
En
Revista:
Cell Death Dis
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Irlanda