The online version of this article (doi:10.1186/ar3398) contains supplementary material, which is available to authorized users.
Yu-Jung Heo, Hye-Jwa Oh, Young Ok Jung, Mi-La Cho contributed equally to this work.
The authors declare that they have no competing interests.
YJH, YOJ, and MLC contributed to conception and design, acquisition of data, analysis and interpretation of data, drafting of the article and final approval of the submitted manuscript. OHJ, JGY and SYL contributed to immunohistochemistry. HRK, MKP and SHL helped with PCR, Western blotting and ELISA, and SHP and HYK contributed cell culture and transfection. All authors approved the final manuscript.
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.
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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
Young Ok Jung
- BioMed Central
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