2004 Fiscal Year Final Research Report Summary
The development of MIF vaccine and its therapeutic effect on murine arthritis model
| Project/Area Number |
15591560
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Hokkaido University |
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Principal Investigator |
ONODERA Shin Hokkaido University Hospital, assistant professor, 病院, 助手 (00359481)
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| Co-Investigator(Kenkyū-buntansha) |
KOYAMA Yoshikazu Hokkaido University, Grad.School of Medicine, assistant professor, 大学院・医学研究科, 助手 (90186841)
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| Project Period (FY) |
2003 – 2004
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| Keywords | macrophage migration inhibitory factor / DNA vaccine / rheumatoid arthritis |
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| Research Abstract |
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).
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Research Products
(11 results)
