Ubiquitin-specific protease 14 regulates LPS-induced inflammation by increasing ERK1/2 phosphorylation and NF-κB activation.
Mol Cell Biochem
; 431(1-2): 87-96, 2017 Jul.
Article
en En
| MEDLINE
| ID: mdl-28364380
ABSTRACT
Persistent activation of nuclear factor B (NF-κB) is very important in the modulation of macrophages cellular response to microbial infections. The deubiquitinase USP14, which is critical for ubiquitin-mediated proteasomal degradation of proteins, is known to be involved in cancer, neurological diseases, and aging. However, the mechanism by which USP14 regulates inflammation remains unclear. Here, we demonstrated that decreasing the deubiquitinase activity of USP14 resulted in reduced lipopolysaccharides (LPS)-mediated tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 release in THP-1 and RAW264.7 cells. Meanwhile, USP14 knockdown by siRNA showed the same effects, with no cytotoxicity in THP-1 cells. Moreover, inhibiting the deubiquitinase activity of USP14 or USP14 knockdown resulted in decreased ERK1/2 and IκBα phosphorylation, increased amounts of the NF-κB inhibitor IκBα, and reduced NF-κB p65 transport from the cytoplasm into nucleus. These findings suggested that USP14 induces NF-κB activity and ERK1/2 phosphorylation triggered by microbial infection.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Lipopolisacáridos
/
Proteína Quinasa 1 Activada por Mitógenos
/
Sistema de Señalización de MAP Quinasas
/
Ubiquitina Tiolesterasa
/
Proteína Quinasa 3 Activada por Mitógenos
/
Factor de Transcripción ReIA
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Cell Biochem
Año:
2017
Tipo del documento:
Article