Inhibition of inflammatory mediators and related signaling pathways by macrophage-stimulating protein in rheumatoid arthritis synovial fibroblasts.
Inflamm Res
; 60(9): 823-9, 2011 Sep.
Article
em En
| MEDLINE
| ID: mdl-21528357
ABSTRACT
OBJECTIVE:
To evaluate the mechanism of macrophage-stimulating protein (MSP)-mediated inhibition of inflammatory cytokine and chemokine production in rheumatoid arthritis synovial fibroblasts (RASF). MATERIALS ANDMETHODS:
RASF were treated with different concentrations (0, 0.5, 1, 5 and 10 ng/ml) of MSP with or without 1 µg/mL lipopolysaccharide (LPS). The protein expressions of IL-1ß, TNF-α, IL-18, MIP-1, MCP-1, RANTES and PGE(2) were analyzed by enzyme-linked immunosorbent assays (ELISA). The total nitric oxide (NO) concentration was determined using the Griess reaction. The protein expressions of iNOS, COX-2, NF-κB(p-p65), IKB-α, IKB-ß, p-P38, p-Erk1/2 (P-P42/44) and p-AKT were detected by Western blotting.RESULTS:
MSP markedly inhibited expression of inflammatory cytokines (IL-1ß, TNF-α and IL-18), chemokines (MIP-1, MCP-1 and RANTES) and iNOS, NO, COX-2 and PGE(2) in RASF stimulated by LPS. MSP treatment decreased expressions of p-IκBα, p-IKBß and p-P65 in RASF in a concentration-dependent manner. Expressions of p-AKT, p-p38 and p-Erk1/2 were also inhibited markedly in RASF stimulated by LPS after treatment with MSP in a concentration-dependent manner.CONCLUSION:
MSP could inhibit the inflammatory cycle by suppressing inflammatory mediators and activation of NF-κB as well. The inhibitory effect of MSP on LPS-stimulated RASF may act through suppression of multiple signals such as the PI3K/AKT and/or MAPK pathways.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
/
Membrana Sinovial
/
Transdução de Sinais
/
Proteínas Proto-Oncogênicas
/
Fator de Crescimento de Hepatócito
/
Mediadores da Inflamação
/
Fibroblastos
Limite:
Humans
Idioma:
En
Revista:
Inflamm Res
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
PATOLOGIA
Ano de publicação:
2011
Tipo de documento:
Article