Upregulation of Macrophage Migration Inhibitory Factor (MIF) Production by Engagement of Toll-like Receptor 3 (TLR3) on Fibroblast-like Synoviocyte (FLS) from Patients with Rheumatoid Arthritis.
10.4078/jkra.2009.16.2.123
- Author:
Yang Mi HER
1
;
Sung Hwan PARK
;
Mi Kyung PARK
;
Hye Jwa OH
;
Kwi Young KANG
;
Mi La CHO
Author Information
1. The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Rheumatoid arthritis;
Fibroblast-like synoviocytes;
Macrophage migration inhibitory factor;
Toll-like receptor engagement
- MeSH:
Antibodies, Neutralizing;
Arthritis, Rheumatoid;
Autoimmune Diseases;
Cytokines;
Enzyme-Linked Immunosorbent Assay;
Humans;
Immunohistochemistry;
Interleukin-6;
Ligands;
Macrophages;
Toll-Like Receptor 3;
Toll-Like Receptors;
Up-Regulation
- From:The Journal of the Korean Rheumatism Association
2009;16(2):123-132
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
OBJECTIVE: Rheumatoid arthritis (RA) is a chronic autoimmune disease. Macrophage migration inhibitory factor (MIF) has been shown to be an important pro-inflammatory cytokine in RA. The aim of this study was to determine if the engagement of toll-like receptor 3 (TLR3) induces the production of MIF in the fibroblast-like synoviocytes (FLS) of patients with RA. METHODS: The expression of inflammatory cytokines (e.g. MIF, IL-6, IL-1beta and TNFalpha) and toll-like receptors (e.g. TLR2, TLR3 and TLR4) in the synovial tissue were quantified by immunohistochemistry. FLS were isolated from the synovial tissues of patients with RA and stimulated with TLR-3 ligand polyI:C, in the presence of a neutralizing antibody against IL-6. The concentrations of MIF and IL-6 in the culture supernatants from the FLS were measured using sandwich ELISA. RESULTS: The engagement of TLR3 with PolyI:C increased the production of MIF in FLS. The stimulatory effect of these TLR ligands showed a dose-dependent trend. The combination of TLR3 and TLR4 synergistically increased the level of MIF and IL-6 production. The addition of neutralizing antibodies against IL-6 abrogated the stimulatory effect of the ligands of TLR3 and TLR4 on the production of MIF. CONCLUSION: These results show that TLR3 engagement stimulates the production of MIF and IL-6. Therefore, the TLRs help perpetuate of RA pathogenesis through production of MIF from the FLS in patients with RA, and might provide a new therapeutic approach for the treatment of rheumatoid arthritis.
