Journal
ONCOTARGET
Volume 7, Issue 47, Pages 76354-76361Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.13047
Keywords
erythroid differentiation regulator 1 (Erdr1); rheumatoid arthritis; inflammation; interleukin-18 (IL-18); synovial fibroblast migration; Immunology and Microbiology Section; Immune response; Immunity
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Funding
- Korea Drug Development Fund (KDDF) - Ministry of Science, ICT and Future Planning, Ministry of Trade, Industry & Energy and Ministry of Health & Welfare (Republic of Korea) [KDDF-201404-04]
- Korea Evaluation Institute of Industrial Technology (KEIT) [KDDF-201404] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and multiple inflammatory cytokines are involved in RA pathogenesis. Interleukin (IL)-18, in particular, has a significant positive correlation with RA. In this study, we investigated the effect of erythroid differentiation regulator 1 (Erdr1), which is negatively regulated by IL-18, in an animal model of inflammatory arthritis, collagen-induced arthritis (CIA) in DBA/1J mice. Treatment of mice with recombinant (r) Erdr1 significantly suppressed the severity of arthritis, histologic features of arthritic tissue, and serum levels of anti-collagen autoantibodies (IgG, IgG1, IgG2a and IgM) in CIA. In addition, IL-18 expression was reduced in the affected synovium of rErdr1-treated mice. Interestingly, Erdr1 treatment suppressed migration in contrast to the pro-migratory effect of IL-18, indicating the therapeutic effects of Erdr1 on CIA through inhibiting synovial fibroblast migration. In addition, Erdr1 inhibited activation of ERK1/2, a key signaling pathway in migration of various cell types. Taken together, these data show that rErdr1 exerts therapeutic effects on RA by inhibiting synovial fibroblast migration, suggesting that rErdr1 treatment might be an effective therapeutic approach for RA.
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