Palmitoylation of NLRP3 Modulates Inflammasome Activation and Inflammatory Bowel Disease Development.
J Immunol
; 213(4): 481-493, 2024 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-38949555
ABSTRACT
Aberrant activity of NLRP3 has been shown associations with severe diseases. Palmitoylation is a kind of protein post-translational modification, which has been shown to regulate cancer development and the innate immune system. Here, we showed that NLRP3 is palmitoylated at Cys419 and that palmitoyltransferase ZDHHC17 is the predominant enzyme that mediates NLRP3 palmitoylation and promotes NLRP3 activation by interacting with NLRP3 and facilitating NIMA-related kinase 7 (NEK7)-NLRP3 interactions. Blockade of NLRP3 palmitoylation by a palmitoylation inhibitor, 2-bromopalmitate, effectively inhibited NLRP3 activation in vitro. Also, in a dextran sulfate sodium-induced colitis model in mice, 2-bromopalmitate application could attenuate weight loss, improve the survival rate, and rescue pathological changes in the colon of mice. Overall, our study reveals that palmitoylation of NLPR3 modulates inflammasome activation and inflammatory bowel disease development. We propose that drugs targeting NLRP3 palmitoylation could be promising candidates in the treatment of NLRP3-mediated inflammatory diseases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aciltransferases
/
Doenças Inflamatórias Intestinais
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Colite
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Lipoilação
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Inflamassomos
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Proteína 3 que Contém Domínio de Pirina da Família NLR
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China