NLRP12 Promotes Mouse Neutrophil Differentiation through Regulation of Non-canonical NF-κB and MAPKERK1/2 Signaling.
Int J Biol Sci
; 14(2): 147-155, 2018.
Article
em En
| MEDLINE
| ID: mdl-29483833
ABSTRACT
Neutrophils are the most important component of the innate immune system. Mechanistic understanding of the mechanism underlying neutrophil differentiation remains elusive. Using genome-wide RNA-seq, we identified genes whose expression is dramatically up-regulated during neutrophil differentiation. Among them is nucleotide-binding leucine-rich repeat and pyrindomain-containing receptor 12 (NLRP12), which plays a role in immune inflammatory responses. Genetic ablation of NLRP12 suppresses NF-κB inducing kinase (NIK) stabilization, RelB nuclear translocation and neutrophil differentiation in vitro. At a mechanistic level, NLRP12 inhibits the activity of mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinases (ERK1/2), relieves ERK1/2 suppression of NIK protein levels. Thus, NLRP12 enhances noncanonical NF-κB signaling through inhibition of ERK1/2 signaling, thereby promoting neutrophil differentiation.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
NF-kappa B
/
Sistema de Sinalização das MAP Quinases
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Peptídeos e Proteínas de Sinalização Intracelular
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Neutrófilos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Int J Biol Sci
Assunto da revista:
BIOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China