Prostaglandin E2 induces dual-specificity phosphatase-1, thereby attenuating inflammatory genes expression in human osteoarthritic synovial fibroblasts.
Prostaglandins Other Lipid Mediat
; 154: 106550, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33857603
ABSTRACT
Characteristic features of osteoarthritis (OA) are joint pain and cartilage degeneration. The degeneration is caused by excess induction of matrix metalloproteinases (MMPs) and the pain is caused by nerve growth factor (NGF)-dependent nerve invasion into synovial tissue in addition to nociceptive pain by prostaglandin (PG)E2. The objective of this study was to clarify the suppressive mechanism of PGE2 on the regulation of MMPs and NGF by focusing on mitogen-activated protein kinases (MAPKs) and their endogenous phosphatase, dual-specificity phosphatase (DUSP)-1 in human synovial fibroblasts. PGE2 strongly increased DUSP-1 and suppressed IL-1ß-induced MAPKs phosphorylation. Inhibition of MAPKs by selective inhibitors differentially regulated the IL-1ß-induced expression of MMPs and NGF expression. IL-1ß-induced MAPKs phosphorylation was prolonged and enhanced in DUSP-1 knockdown cells and the expression of MMPs and NGF was also increased. This study revealed that PGE2 has novel biological activity that suppresses NGF and MMPs expression by inducing DUSP-1 expression.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interleucina-1beta
Idioma:
En
Revista:
Prostaglandins Other Lipid Mediat
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Japão