THU0007 IL-26 PROMOTES OSTEOCLASTOGENESIS IN RHEUMATOID ARTHRITIS

Abstract

Background: IL-26 is a 171-amino acid protein, which is classified as a member of the Th17 cytokine family. The role of IL-26 in osteoclastogenesis in RA is needed to be clarified to understand the pathogenesis of RA. Objectives: To examine the functional role of interleukin-26 (IL-26) in the expression of RANKL and induction of osteoclastogenesis in rheumatoid arthritis (RA). Methods: The expression of IL-20Rα, CD55 and RANKL in RA synovial fibroblasts was analyzed using confocal microscopy. RA Fibroblasts like synoviocytes (RA-FLS) were treated with recombinant human IL-26, and the expression of RANKL messenger RNA (mRNA) and protein was measured using real-time polymerase chain reaction and ELISA. Human peripheral blood monocytes were cultured with macrophage colony-stimulating factor and IL-26, after which osteoclastogenesis was evaluated by counting the number of tartrateresistant acid phosphataseepositive multinucleated cells. Osteoclastogenesis was also evaluated after monocytes were co-cultured with IL-26-prestimulated FLS. Results: The IL-26 concentration in the FLS was higher in RA patients than in patients with osteoarthritis (OA). In RA-FLS treated with rhIL-26, the expression of RANKL mRNA and protein was increased in a dose-dependent manner. IL-26 increased the expression of RANKL in RA-FLS, and the IL-26-induced RANKL expression decreased by the inhibition of IL-20Rα. IL-26–induced RANKL expression was down-regulated significantly by the inhibition of SHP-1, ERK, JNK, stat1, c-jun or p38 MAPK/NF-κB signaling. When monocytes isolated from human peripheral blood were cultured with IL-26, they were differentiated into osteoclasts in the absence of RANKL. Monocytes were also differentiated into osteoclasts when they were cocultured with IL-26–pretreated RA-FLS Conclusion: IL-26 has a dual effect on osteoclastogenesis in RA: 1) direct induction of osteoclastogenesis from monocytes and 2) up-regulation of RANKL production in RA-FLS. This IL-26/RANKL axis could be a potential therapeutic target for bone destruction in RA. Reference: [1] Corvaisier M, Delneste Y, Jeanvoine H, et al. IL-26 Is Overexpressed in Rheumatoid Arthritis and Induces Proinflammatory Cytokine Production and Th17 Cell Generation. PLoS Biol. 2012;10(9):e1001395. Acknowledgement: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT and Future Planning (NRF-2017R1A2B4006015, NRF-2018R1D1A1A02050982 and NRF-2018R1A2B2006820) Disclosure of Interests: None declared