IL-17 and Toll-like Receptor 2 or Toll-like Receptor 4 Combined Engagement Upregulates RANKL and IL-6 in Human Rheumatoid Synovial Fibroblasts.
10.4078/jkra.2010.17.1.36
- Author:
Kyoung Woon KIM
1
;
Sang Heon LEE
;
Mi La CHO
;
Hye Joa OH
;
Yun Ju WOO
;
Suk Hyung KIM
;
Hae Rim KIM
Author Information
1. Division of Rheumatology, Konkuk University School of Medicine, Medical Immunology Center, Institute of Biomedical Science and Technology, Seoul, Korea. shlee@kuh.ac.kr
- Publication Type:Original Article
- Keywords:
Toll-like receptor;
IL-17;
RANKL;
IL-6;
RA FLS
- MeSH:
Blotting, Western;
Fibroblasts;
Humans;
Immunohistochemistry;
Interleukin-17;
Interleukin-6;
Ligands;
Osteoarthritis;
Peptidoglycan;
RNA, Messenger;
Synovial Membrane;
Toll-Like Receptor 2;
Toll-Like Receptor 4;
Toll-Like Receptors
- From:The Journal of the Korean Rheumatism Association
2010;17(1):36-45
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
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.
