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KMID : 0388220100170010036
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Journal of the Korean Rheumatism Association
2010 Volume.17 No. 1 p.36 ~ p.45
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IL-17 and Toll-like Receptor 2 or Toll-like Receptor 4 Combined Engagement Upregulates RANKL and IL-6 in Human Rheumatoid Synovial Fibroblasts
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Kim Kyoung-Woon
Lee Sang-Heon
Cho Mi-La
Oh Hye-Jwa
Woo Yun-Ju
Kim Suk-Hyung
Kim Hae-Rim
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Abstract
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Objective: The aim of this study was to clarify whether stimulation of recombinant IL-17, TLR2 and TLR4 by their specific ligands induces the production of RANKL and IL-6 in the fibroblast-like synoviocytes (FLSs) from RA patients.
Methods: FLSs were isolated from RA synovial tissues and they were stimulated with the IL-17, TLR2 ligand bacterial peptidoglycan (PGN) and TLR4 ligand lipopolysaccharide (LPS). The RANKL levels were assessed by RT-PCR and western blotting. The expressions of IL-17, TLR2, TLR4, RANKL and IL-6 in the RA synovium were quantified by immunohistochemistry and these values were compared with the values obtained in the osteoarthritis synovium. The increased IL-6 production in the culture supernatants of the RA FLSs was quantified by sandwich ELISA.
Results: The mRNA and protein levels of RANKL and IL-6 increased in the RA FLSs stimulated with PGN, LPS and IL-17, or PGN plus IL-17 or LPS plus IL-17. The expressions of IL-17, TLR2, TLR4, RANKL and IL-6 were much higher in the RA synovium than those in the osteoarthritis (OA) synovium.
Conclusion: We observed synergistic effects of TLR-2, TLR-4 and IL-17 upon the induction of RANKL. In conclusion, our data supports the previous evidence of an important role of TLR-2, TLR-4 and IL-17 in the pathogenesis of RA.
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KEYWORD
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Toll-like receptor, IL-17, RANKL, IL-6, RA FLS
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