Pharmacological inhibition of IKKß dampens NLRP3 inflammasome activation after priming in the human myeloid cell line THP-1.
Biochem Biophys Res Commun
; 545: 177-182, 2021 03 19.
Article
en En
| MEDLINE
| ID: mdl-33561652
ABSTRACT
The NLRP3 inflammasome is a critical component of the innate immune response to sterile inflammation. Its regulation involves a priming step, required for up-regulation of inflammasome protagonists and an activation step leading to NLRP3 inflammasome complex assembly, which triggers caspase-1 activity. The IκKß kinase regulates canonical NF-κB, a key pathway involved in transcriptional priming. We found that IκKß also regulates the activation and function of the NLRP3 inflammasome beyond the priming step. Two unrelated IκKß inhibitors, AFN700 and TPCA-1, when applied after priming, fully blocked IL-1ß secretion triggered by nigericin in THP-1 cells. Both inhibitors prevented neither inflammasome assembly, as monitored by measuring the formation of ASC specks, nor the generation of caspase-1 p20, a hallmark of caspase-1 activity, but they impaired the initial cleavage and activation of procaspase-1. These data thus indicate that IκKß activity is required for efficient activation of NLRP3, suggesting that IκKß may fulfill a dual role in coupling priming and activation of the NLRP3 inflammasome.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Quinasa I-kappa B
/
Inflamasomas
/
Proteína con Dominio Pirina 3 de la Familia NLR
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2021
Tipo del documento:
Article
País de afiliación:
Suiza