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The expression of the receptor for advanced glycation end-products (RAGE) in RA-FLS is induced by IL-17 via Act-1

Yu-Jung Heo1, Hye-Jwa Oh1, Young Ok Jung2*, Mi-La Cho14*, Seon-Yeong Lee1, Jun-Geol Yu1, Mi-Kyung Park1, Hae-Rim Kim3, Sang-Heon Lee3, Sung-Hwan Park1 and Ho-Youn Kim1

Author Affiliations

1 The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, 505 Banpo-dong, Seocho-gu, Seoul 137-040, South Korea

2 Division of Rheumatology, Department of Internal Medicine, Hallym University Kang-Nam Sacred Heart Hospital, Seoul, 143-729, Korea

3 Division of Rheumatology, Department of Internal Medicine, Konkuk University School of Medicine, 4-12, Hwayang-dong, Gwangjin-gu, Seoul, 143-729, Korea

4 Immune Tolerance Research Center, Convergent Research Consortium for Immunologic disease (CRCID), The Catholic University of Korea College of Medicine, St Mary's Hospital, 505 Banpo-dong Seocho-Gu, Seoul, 137-701, Korea

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Arthritis Research & Therapy 2011, 13:R113  doi:10.1186/ar3398

Published: 12 July 2011



The receptor for advanced glycation end-products (RAGE) has been implicated in the pathogenesis of arthritis. We conducted this study to determine the effect of interleukin (IL)-17 on the expression and production of RAGE in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). The role of nuclear factor-κB (NF-κB) activator 1 (Act1) in IL-17-induced RAGE expression in RA-FLS was also evaluated.


RAGE expression in synovial tissues was assessed by immunohistochemical staining. RAGE mRNA production was determined by real-time polymerase chain reaction. Act-1 short hairpin RNA (shRNA) was produced and treated to evaluate the role of Act-1 on RAGE production.


RAGE, IL-17, and Act-1 expression increased in RA synovium compared to osteoarthritis synovium. RAGE expression and production increased by IL-17 and IL-1β (*P <0.05 vs. untreated cells) treatment but not by tumor necrosis factor (TNF)-α in RA-FLS. The combined stimuli of both IL-17 and IL-1β significantly increased RAGE production compared to a single stimulus with IL-17 or IL-1β alone (P <0.05 vs. 10 ng/ml IL-17). Act-1 shRNA added to the RA-FLS culture supernatant completely suppressed the enhanced production of RAGE induced by IL-17.


RAGE was overexpressed in RA synovial tissues, and RAGE production was stimulated by IL-17 and IL-1β. Act-1 contributed to the stimulatory effect of IL-17 on RAGE production, suggesting a possible inhibitory target for RA treatment.