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

MIF疫苗的研制及其对小鼠关节炎模型的治疗作用

基本信息

批准号：
15591560
负责人：
ONODERA Shin
金额：
$ 2.24万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

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).

1）我们证明，巨噬细胞迁移抑制因子（MIF）上调类风湿关节炎（RA）患者滑膜成纤维细胞中IL-8和IL-1β mRNA的表达，并且这种诱导是由酪氨酸激酶、PKC以及转录因子Ap-1和NF-κB介导的。 (Arthritis Rheum 2004)。2)我们研究了MIF在小鼠胶原抗体诱导的关节炎(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 的发作而增强。在用多克隆抗MIF抗体预处理的野生型小鼠和MIF-/-小鼠中，关节炎高峰期的组织病理学评分显着降低（与用非免疫IgG预处理的野生型小鼠相比，p<0.05）。与此相关，两组中 MMP-13 和 MIP-2 的 mRNA 表达以及踝关节炎症细胞的浸润均受到抑制。 (Cytokine 2004)。3)针对MIF的RA新治疗方法；我们尝试了 MIF-DNA 疫苗接种方法。通过引入编码破伤风毒素、卵清蛋白和鸡蛋清溶菌酶的T_H表位对鼠MIF cDNA进行部分修饰，将其克隆到pcDNA3中并制备成MIF-DNA疫苗。通过电穿孔将它们递送至 8w-Balb/c 小鼠后，引入 CAIA。在用 MIF-DNA 疫苗预处理的小鼠中，关节炎高峰期的组织病理学评分显着降低（与用对照载体预处理的小鼠相比，p<0.05）。尽管正在开发中，但该方法有望成为 RA 的一种新型治疗方法（正在准备中）。

项目成果

期刊论文数量（36）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Transtrochanteric rotational osteotomy for osteonecrosis of femoral head : Relationship between radiographic features and secondary collapse.

经转子旋转截骨术治疗股骨头坏死：放射学特征与继发性塌陷之间的关系。

DOI：
发表时间：
期刊：
J Orthop Sci (in press)
影响因子：
0
作者：
Onodera S;Majima T;Abe Y;Ito H;Matsuno T;Minami A
通讯作者：
Minami A

Macrophage migration inhibitory factor (MIF) up-regulates expression of interleukin (IL)-8 mRNA in synovial fibroblasts of rheumatoid arthritis. Common transcriptional regulatory mechanism between IL-8 and IL-1β.

巨噬细胞迁移抑制因子 (MIF) 上调类风湿性关节炎滑膜成纤维细胞中白细胞介素 (IL)-8 mRNA 的表达 IL-8 和 IL-1β 之间的共同转录调节机制。

DOI：
发表时间：
2004
期刊：
Arthritis Rheum 50
影响因子：
0
作者：
Onodera;S.
通讯作者：
S.

Inhibition of joint inflammation and destruction induced by anti-type II collagen antibody/lipopolysaccharide (LPS)-induced arthritis in mice due to deletion of macrophage migration inhibitory factor (MIF)

DOI：
10.1016/j.cyto.2004.02.007
发表时间：
2004-06-07
期刊：
CYTOKINE
影响因子：
3.8
作者：
Ichiyama, H;Onodera, S;Tohyama, H
通讯作者：
Tohyama, H

Transtrochanteric rotational osteotomy for osteonecrosis of femoral head ; Relationship between radiographic features and secondary collapse.

经转子旋转截骨术治疗股骨头坏死；

DOI：
发表时间：
期刊：
J Orthop Sci (in press)
影响因子：
0
作者：
Ichiyama H;Onodera S;Nishihira J;Ishibashi T;Nakayama T;Minami A;Yasuda K;Tohyama H;Shin Onodera;Shin Onodera;Hiroki Ichiyama;Shin Onodera
通讯作者：
Shin Onodera

Up-regulation of macrophage migration-inhibitory factor expression after compression-induced spinal cord injury in rats