The development of MIF vaccine and its therapeutic effect on murine arthritis model

1)我们发现巨噬细胞移动抑制因子上调类风湿性关节炎(RA)患者滑膜成纤维细胞中IL-8和IL-1β的表达，并且这种诱导是由酪氨酸激酶、蛋白激酶C、转录因子AP-1和NF-κB介导的(Artis Rheum，2004年)。2)探讨MIF在胶原抗体诱导的小鼠关节炎(CAIA)模型中的作用。在野生型(Wt)小鼠中，MIF、MMP-13和MIP-2的mRNA表达随着CAIA的发生而增强。在多克隆抗MIF抗体处理的wt小鼠和MIF-/-小鼠中，关节炎高峰期的组织病理学评分显著降低(p&lt；0.05，vs.wt-小鼠)。与此相关的是，两组大鼠踝关节中的炎性细胞浸润和基质金属蛋白酶-13、MIP-2mRNA的表达均受到抑制。(细胞因子2004)。3)以MIF为靶点治疗类风湿关节炎的新途径我们尝试了MIF-DNA疫苗接种方法。通过引入编码破伤风毒素、卵清蛋白和蛋清溶菌酶的T_H表位对小鼠MIF基因进行部分修饰，将其克隆到pcDNA3中，制备成MIF-DNA疫苗。用电穿孔法将其导入8w-Balb/c小鼠后，引入CAIA。在MIF-DNA疫苗预处理的小鼠中，关节炎高峰时的组织病理学评分显著降低(p&lt；0.05，与对照载体预处理的小鼠相比)。虽然该方法仍在开发中，但作为RA的一种新的治疗方法(正在准备中)很有希望。

1)We demonstrated that macrophage migration inhibitory factor (MIF) up-regulates IL-8 and IL-1β mRNA expression in synovial fibroblasts of rheumatoid arthritis (RA) patients, and that this induction is mediated by tyrosine kinase, PKC, and transcription factors Ap-1 and NF-κB. (Arthritis Rheum 2004)。2)We investigated the involvement of MIF in murine collagen-antibody induced arthritis (CAIA) model. In wild-type (wt) mice, the mRNA expression of MIF, MMP-13, and MIP-2 were enhanced in association with the onset of CAIA. In wt-mice pretreated with polyclonal anti-MIF antibody and in MIF-/-mice, the histopathological scores at the peak of arthritis were significantly reduced (p<0.05, v.s. wt-mice pretreated with nonimmune IgG). In association with this, the mRNA expression of MMP-13 and MIP-2 and infiltration of inflammatory cells in ankle joints were suppressed in the two groups. (Cytokine 2004)。3)A novel therapeutic approach for RA targeting MIF ; We attempted MIF-DNA vaccination methods. Murine MIF cDNA, modified in part by introducing T_H epitopes that encodes tetanus toxin, ovalbumin, and hen egg white-lysozyme, was cloned into pcDNA3 and prepared as MIF-DNA vaccine. After delivery of them to 8w-Balb/c mice by electroporation, CAIA was introduced. In mice pretreated with MIF-DNA vaccine, the histopathological scores at the peak of arthritis were significantly reduced (p<0.05, v.s. mice pretreated with control vector). Although under way of development, this method is promising as a novel therapeutic approach for RA (in preparation).