Induction of Macrophage Migration Inhibitory Factor in ConA-Stimulated Rheumatoid Arthritis Synovial Fibroblasts through the P38 MAP Kinase-Dependent Signaling Pathway
The Korean Journal of Internal Medicine
; : 317-326, 2010.
Article
em En
| WPRIM
| ID: wpr-103224
Biblioteca responsável:
WPRO
ABSTRACT
BACKGROUND/AIMS: This study was undertaken to identify the intracellular signaling pathway involved in induction of macrophage migration inhibitory factor (MIF) in human rheumatoid arthritis (RA) synovial fibroblasts. METHODS: Human RA synovial fibroblasts were treated with concanavalin A (ConA), various cytokines, and inhibitors of signal transduction molecules. The production of MIF by synovial fibroblasts was measured in culture supernatants by ELISA. The expression of MIF mRNA was determined using reverse transcriptase polymerase chain reaction (RT-PCR) and real-time PCR. Phosphorylation of p38 mitogen-activated protein (MAP) kinase in synovial fibroblasts was confirmed using Western blotting. The expression of MIF and p38 MAP kinase in RA synovium was determined using dual immunohistochemistry. RESULTS: The production of MIF by RA synovial fibroblasts increased in a dose-dependent manner after ConA stimulation. MIF was also induced by interferon-gamma, CD40 ligand, interleukin-15, interleukin-1beta, tumor necrosis factor-alpha, and transforming growth factor-beta. The production of MIF by RA synovial fibroblasts was significantly reduced after inhibition of p38 MAP kinase. The expression of MIF and p38 MAP kinase was upregulated in the RA synovium compared with the osteoarthritis synovium. CONCLUSIONS: These results suggest that MIF production was induced through a p38 MAP-kinase-dependent pathway in RA synovial fibroblasts.
Palavras-chave
Texto completo:
1
Base de dados:
WPRIM
Assunto principal:
Artrite Reumatoide
/
Membrana Sinovial
/
RNA Mensageiro
/
Sequência de Bases
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Transdução de Sinais
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Células Cultivadas
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Citocinas
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Fatores Inibidores da Migração de Macrófagos
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Primers do DNA
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Concanavalina A
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
The Korean Journal of Internal Medicine
Ano de publicação:
2010
Tipo de documento:
Article