Impact of NF-κB pathway on the apoptosis-inflammation-autophagy crosstalk in human degenerative nucleus pulposus cells.
Aging (Albany NY)
; 11(17): 7294-7306, 2019 09 13.
Article
en En
| MEDLINE
| ID: mdl-31518335
ABSTRACT
The NF-κB pathway has been reported to play a very important role in the process of intervertebral disc degeneration (IVDD). Our results demonstrated that knockdown of NF-κB with P65-siRNA can significantly decrease cell apoptosis and the expression of pro-inflammation factors TNF-α and IL-1ß in LPS-induced nucleus pulposus cells (NPCs). However, the molecular mechanism of NF-κB pathway exerting anti-inflammation and anti-apoptosis function remains unclear. Some researchers reported that inhibiting NF-κB pathway can attenuate the catabolic effect by promoting autophagy during inflammatory conditions in rat nucleus pulposus cells. Therefore, we hypothesized that in human NPCs, inhibiting NF-κB pathway may also promote autophagy. Our results indicated that after knockdown of NF-κB, the autophagy was significantly increased and the expression of p-AKT and p-mTOR protein markedly decreased, but the level of autophagy was inhibited after treatment with AKT activator SC79, suggesting the involvement of AKT/mTOR-mediated autophagy was under autophagy activation. However, both LPS-induced NPCs apoptosis and expression of pro-inflammation factors were further increased by pretreatment with the autophagy inhibitor chloroquine (CQ). These suggested that inhibiting NF-κB pathway can promote autophagy and decrease apoptosis and inflammation response in LPS-induced NPCs. Meanwhile, autophagy triggered by NF-κB inhibition plays a protective role against apoptosis and inflammation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
FN-kappa B
/
Degeneración del Disco Intervertebral
/
Núcleo Pulposo
Tipo de estudio:
Observational_studies
Límite:
Humans
Idioma:
En
Revista:
Aging (Albany NY)
Asunto de la revista:
GERIATRIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
China