DUSP-1 Induced by PGE2 and PGE1 Attenuates IL-1ß-Activated MAPK Signaling, Leading to Suppression of NGF Expression in Human Intervertebral Disc Cells.
Int J Mol Sci
; 23(1)2021 Dec 29.
Article
em En
| MEDLINE
| ID: mdl-35008797
ABSTRACT
The molecular mechanism of discogenic low back pain (LBP) involves nonphysiological nerve invasion into a degenerated intervertebral disc (IVD), induced by nerve growth factor (NGF). Selective cyclooxygenase (COX)-2 inhibitors are mainly used in the treatment of LBP, and act by suppressing the inflammatory mediator prostaglandin E2 (PGE2), which is induced by inflammatory stimuli, such as interleukin-1ß (IL-1ß). However, in our previous in vitro study using cultured human IVD cells, we demonstrated that the induction of NGF by IL-1ß is augmented by a selective COX-2 inhibitor, and that PGE2 and PGE1 suppress NGF expression. Therefore, in this study, to elucidate the mechanism of NGF suppression by PGE2 and PGE1, we focused on mitogen-activated protein kinases (MAPKs) and its phosphatase, dual-specificity phosphatase (DUSP)-1. IL-1ß-induced NGF expression was altered in human IVD cells by MAPK pathway inhibitors. PGE2 and PGE1 enhanced IL-1ß-induced DUSP-1 expression, and suppressed the phosphorylation of MAPKs in human IVD cells. In DUSP-1 knockdown cells established using small interfering RNA, IL-1ß-induced phosphorylation of MAPKs was enhanced and prolonged, and NGF expression was significantly enhanced. These results suggest that PGE2 and PGE1 suppress IL-1ß-induced NGF expression by suppression of the MAPK signaling pathway, accompanied by increased DUSP-1 expression.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Alprostadil
/
Dinoprostona
/
Fator de Crescimento Neural
/
Sistema de Sinalização das MAP Quinases
/
Interleucina-1beta
/
Fosfatase 1 de Especificidade Dupla
/
Disco Intervertebral
Limite:
Adult
/
Aged
/
Aged80
/
Humans
/
Middle aged
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article