The TRIF-RIPK1-Caspase-8 signalling in the regulation of TLR4-driven gene expression.
Immunology
; 172(4): 566-576, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38618995
ABSTRACT
The inflammatory response is tightly regulated to eliminate invading pathogens and avoid excessive production of inflammatory mediators and tissue damage. Caspase-8 is a cysteine protease that is involved in programmed cell death. Here we show the TRIF-RIPK1-Caspase-8 is required for LPS-induced CYLD degradation in macrophages. TRIF functions in the upstream of RIPK1. The homotypic interaction motif of TRIF and the death domain of RIPK1 are essential for Caspase-8 activation. Caspase-8 cleaves CYLD and the D235A mutant is resistant to the protease activity of Caspase-8. TRIF and RIPK1 serve as substrates of Capase-8 in vitro. cFLIP interacts with Caspase-8 to modulate its protease activity on CYLD and cell death. Deficiency in TRIF, Caspase-8 or CYLD can lead to a decrease or increase in the expression of genes encoding inflammatory cytokines. Together, the TRIF-Caspase-8 and CYLD play opposite roles in the regulation of TLR4 signalling.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Lipopolissacarídeos
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Proteínas Adaptadoras de Transporte Vesicular
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Receptor 4 Toll-Like
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Caspase 8
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Proteína Serina-Treonina Quinases de Interação com Receptores
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Enzima Desubiquitinante CYLD
Limite:
Animals
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Humans
Idioma:
En
Revista:
Immunology
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China