Therapeutic effect of erythroid differentiation regulator 1 (Erdr1) on collagen-induced arthritis in DBA/1J mouse.
Therapeutic effect of erythroid differentiation regulator 1 (Erdr1) on collagen-induced arthritis in DBA/1J mouse.
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DOI：
10.18632/oncotarget.13047
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发表时间：
2016-11-22
期刊：
影响因子：
--
通讯作者：
Cho D
中科院分区：
文献类型：
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作者：
Kim KE;Kim S;Park S;Houh Y;Yang Y;Park SB;Kim S;Kim D;Hur DY;Kim S;Park HJ;Bang SI;Cho D
类风湿性关节炎（RA）是一种慢性炎症性自身免疫性疾病，多种炎性细胞因子参与了RA的发病过程。特别是白细胞介素（IL）-18与RA有显著正相关。在这项研究中，我们研究了红细胞分化调节因子1（Erdr 1），这是负调控的IL-18，在炎症性关节炎，胶原诱导的关节炎（CIA）的动物模型在DBA/1 J小鼠的作用。用重组（r）Erdr 1治疗小鼠显著抑制CIA中关节炎的严重程度、关节炎组织的组织学特征和抗胶原自身抗体（IgG、IgG 1、IgG 2a和IgM）的血清水平。此外，IL-18的表达减少在受影响的滑膜rErdr 1治疗的小鼠。有趣的是，与IL-18的促迁移作用相反，Erdr 1治疗抑制了迁移，表明Erdr 1通过抑制滑膜成纤维细胞迁移对CIA的治疗作用。此外，Erdr 1抑制ERK 1/2的活化，ERK 1/2是各种细胞类型迁移的关键信号通路。综上所述，这些数据表明，rErdr 1通过抑制滑膜成纤维细胞迁移对RA发挥治疗作用，表明rErdr 1治疗可能是RA的有效治疗方法。
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.