cFLIPL protects macrophages from LPS-induced pyroptosis via inhibition of complex II formation.
Science
; 367(6484): 1379-1384, 2020 03 20.
Article
em En
| MEDLINE
| ID: mdl-32193329
ABSTRACT
Cell death and inflammation are interdependent host responses to infection. During pyroptotic cell death, interleukin-1ß (IL-1ß) release occurs through caspase-1 and caspase-11-mediated gasdermin D pore formation. In vivo, responses to lipopolysaccharide (LPS) result in IL-1ß secretion. In vitro, however, murine macrophages require a second "danger signal" for the inflammasome-driven maturation of IL-1ß. Recent reports have shown caspase-8-mediated pyroptosis in LPS-activated macrophages but have provided conflicting evidence regarding the release of IL-1ß under these conditions. Here, to further characterize the mechanism of LPS-induced secretion in vitro, we reveal an important role for cellular FLICE-like inhibitory protein (cFLIP) in the regulation of the inflammatory response. Specifically, we show that deficiency of the long isoform cFLIPL promotes complex II formation, driving pyroptosis, and the secretion of IL-1ß in response to LPS alone.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Complexo II de Transporte de Elétrons
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Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD
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Inflamassomos
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Piroptose
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Ativação de Macrófagos
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Macrófagos
Limite:
Animals
Idioma:
En
Revista:
Science
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos