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KMID : 0388220090160020123
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Journal of the Korean Rheumatism Association
2009 Volume.16 No. 2 p.123 ~ p.132
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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
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Hur Yang-Mi
Park Sung-Hwan
Park Mi-Kyung
Oh Hye-Jwa
Kang Kwi-Young
Cho Mi-La
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Abstract
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Objectives: 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-1β and TNFα) 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.
Conclusions: 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.
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KEYWORD
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Rheumatoid arthritis, Fibroblast-like synoviocytes, Macrophage migration inhibitory factor, Toll-like receptor engagement
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