|Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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).