Induction of Macrophage Migration Inhibitory Factor in ConA-Stimulated Rheumatoid Arthritis Synovial Fibroblasts through the P38 MAP Kinase-Dependent Signaling Pathway.
10.3904/kjim.2010.25.3.317
- Author:
Hae Rim KIM
1
;
Mi Kyung PARK
;
Mi La CHO
;
Kyoung Woon KIM
;
Hye Joa OH
;
Jin Sil PARK
;
Yang Mi HEO
;
Sang Heon LEE
;
Ho Youn KIM
;
Sung Hwan PARK
Author Information
1. Division of Rheumatology, Department of Internal Medicine, Konkuk University School of Medicine Seoul, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Macrophage, migration-inhibitory factors;
Arthritis rheumatoid;
Synovial fibroblast;
p38 mitogen-activated protein kinases
- MeSH:
Arthritis, Rheumatoid/genetics/*metabolism;
Base Sequence;
Cells, Cultured;
Concanavalin A/pharmacology;
Cytokines/pharmacology;
DNA Primers/genetics;
Fibroblasts/drug effects/metabolism;
Humans;
Macrophage Migration-Inhibitory Factors/*biosynthesis/genetics;
RNA, Messenger/genetics/metabolism;
Signal Transduction/drug effects;
Synovial Membrane/drug effects/metabolism;
p38 Mitogen-Activated Protein Kinases/metabolism
- From:The Korean Journal of Internal Medicine
2010;25(3):317-326
- CountryRepublic of Korea
- Language:English
-
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.
