Session Type: Poster Session (Monday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Nuclear factor-kappaB (NF-kappaB) and extracellular-signal-regulated kinase (ERK) have been implicated as a therapeutic target for the treatment of rheumatoid arthritis (RA). Raf kinase inhibitory protein (RKIP), as an upstream regulator for NF-kB and ERK pathways, has been widely explored in the field of cancer. However, the effect of RKIP in RA have not yet been elucidated. Thus, the purpose of this study was to investigate whether RKIP might have anti-arthritic effects.
Methods: The adenovirus containing RKIP complementary DNA (Ad-RKIP) or RKIP shRNA (Ad-shRKIP) were used in fibroblast-like synoviocytes (FLS) of RA patients and mouse models of collagen-induced arthritis (CIA) and K/BxN serum transfer arthritis. Quantitative real-time PCR, phospho-protein array analysis, immunohistochemistry, ELISA, western blotting, TRAP and safranin-O staining, migration and invasion assay were used.
Results: The expression of RKIP were significantly decreased in synovial tissue and FLS of RA compared to osteoarthritis (OA). Ad-RKIP suppressed invasion and migration, chemokine production, and matrix metalloproteinase secretion induced by cytokines (IL 1ß, LPS, TNF α, and TGF ß) in RA FLS. Additionally, RKIP negatively regulated the Raf/MEK/ERK and NF-κB pathway in RA FLS. CIA and K/BxN serum transfer arthritic mice, which were injected with Ad-shRKIP, showed earlier development and exacerbation of arthritis. However, Ad-RKIP treated CIA mice had a lower cumulative incidence and less severe arthritis, based on radiologic and histopathologic findings, and inflammatory cytokine levels, than control virus-injected mice.
Conclusion: These results suggest that using RKIP to block the NF-kappaB and the Raf/MEK/ERK pathway in RA reduce both the inflammatory response and the joint destruction. Thus, RKIP may have therapeutic potential in the prevention and treatment of RA.
To cite this abstract in AMA style:Lee S, Noh H, Cheon Y. RKIP, as an Upstream Regulator of Intracellular Signaling, Exerts Anti-arthritic Effect in Fibroblast-like Synoviocyte and Collagen-induced Arthritis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/rkip-as-an-upstream-regulator-of-intracellular-signaling-exerts-anti-arthritic-effect-in-fibroblast-like-synoviocyte-and-collagen-induced-arthritis/. Accessed May 31, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rkip-as-an-upstream-regulator-of-intracellular-signaling-exerts-anti-arthritic-effect-in-fibroblast-like-synoviocyte-and-collagen-induced-arthritis/