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Macrophage migration inhibitory factor (MIF): genetic evidence for participation in early onset and early stage rheumatoid arthritis.巨噬细胞移动抑制因子（MIF）：参与早发性和早期类风湿关节炎的遗传证据。
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Deletion of macrophage migration inhibitory factor worsens stroke outcome in female mice.巨噬细胞移动抑制因子缺失可加重雌性小鼠脑卒中的预后不良。
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Serum levels of macrophage migration inhibitory factor are associated with rheumatoid arthritis course.巨噬细胞移动抑制因子的血清水平与类风湿关节炎的病程相关。
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DNA vaccination targeting macrophage migration inhibitory factor prevents murine experimental colitis.针对巨噬细胞移动抑制因子的 DNA 疫苗可预防实验性结肠炎。
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Identification of NURR1 as a mediator of MIF signaling during chronic arthritis: effects on glucocorticoid-induced MKP1.鉴定 NURR1 作为慢性关节炎期间 MIF 信号的中介物：对糖皮质激素诱导的 MKP1 的影响。
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一种靶向巨噬细胞移动抑制因子的新型DNA疫苗可保护小鼠关节炎模型的关节免受炎症和破坏。

A novel DNA vaccine targeting macrophage migration inhibitory factor protects joints from inflammation and destruction in murine models of arthritis.

作者信息

Onodera Shin, Ohshima Shigeki, Tohyama Harukazu, Yasuda Kazunori, Nishihira Jun, Iwakura Yoichiro, Matsuda Ikkei, Minami Akio, Koyama Yoshikazu

机构信息

Hokkaido University Graduate School of Medicine, Sapporo, Japan.

出版信息

Arthritis Rheum. 2007 Feb;56(2):521-30. doi: 10.1002/art.22407.

DOI:10.1002/art.22407
PMID:17265487
Abstract

OBJECTIVE

Previous studies have demonstrated that neutralization of macrophage migration inhibitory factor (MIF) by anti-MIF antibodies decreases joint inflammation and destruction in a type II collagen-induced arthritis model in mice. The aim of this study was to develop and describe a simple and effective method of active immunization that induces anti-MIF autoantibodies, which may neutralize MIF bioactivity.

METHODS

We developed a MIF DNA vaccine by introducing oligonucleotides encoding a tetanus toxoid (TTX) Th cell epitope into the complementary DNA sequence of murine MIF. Mice were injected with this construct in conjunction with electroporation. The ability of this immunization to inhibit the development of collagen antibody-induced arthritis (CAIA) in BALB/c mice and spontaneous autoimmune arthritis in interleukin-1 receptor antagonist (IL-1Ra)-deficient mice was then evaluated.

RESULTS

Mice that received the MIF/TTX DNA vaccine developed high titers of autoantibodies that reacted to native MIF. Compared with unvaccinated mice, vaccinated mice also produced less serum tumor necrosis factor alpha after receiving an intravenous injection of lipopolysaccharide. In addition, vaccination with MIF/TTX DNA resulted in significant amelioration of both CAIA in BALB/c mice and symptoms of autoimmune arthritis in IL-1Ra-knockout mice.

CONCLUSION

These results suggest that MIF/TTX DNA vaccination may be useful for ameliorating the symptoms of rheumatoid arthritis.

摘要

目的

先前的研究表明，在小鼠II型胶原诱导的关节炎模型中，抗巨噬细胞移动抑制因子（MIF）抗体中和MIF可减轻关节炎症和破坏。本研究的目的是开发并描述一种简单有效的主动免疫方法，该方法可诱导产生抗MIF自身抗体，从而中和MIF的生物活性。

方法

我们通过将编码破伤风类毒素（TTX）Th细胞表位的寡核苷酸引入小鼠MIF的互补DNA序列中，开发了一种MIF DNA疫苗。将该构建体与电穿孔结合注射到小鼠体内。然后评估这种免疫接种抑制BALB/c小鼠胶原抗体诱导的关节炎（CAIA）以及白细胞介素-1受体拮抗剂（IL-1Ra）缺陷小鼠的自发性自身免疫性关节炎发展的能力。

结果

接受MIF/TTX DNA疫苗的小鼠产生了高滴度的与天然MIF反应的自身抗体。与未接种疫苗的小鼠相比，接种疫苗的小鼠在静脉注射脂多糖后产生的血清肿瘤坏死因子α也更少。此外，用MIF/TTX DNA进行疫苗接种可显著改善BALB/c小鼠的CAIA以及IL-1Ra基因敲除小鼠的自身免疫性关节炎症状。

结论

这些结果表明，MIF/TTX DNA疫苗接种可能有助于改善类风湿性关节炎的症状。