| Budget Amount *help |
¥3,620,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Macrophage migration inhibitory factor (MIF) was originally identified as a cytokine-derived activated T lymphocyte in vitro. Moreover, MIF is released from a variety of cells in response to stimuli as a proinflammatory cytokine. MIF plays an important role in the pathogenesis of inflammatory diseases. The serum and the local expression of MIF are significantly upregulated in inflammatory diseases. It is of note that neutralization of MIF activity by the anti-MIF antibody ameliorated inflammation in these experimental models.
On the other hand, it has been reported that MIF is increased in the sera of patients with human IBD and experimental colitis. Although these results suggest that MIF plays a critical role in inflammation in the colon, the molecular basis of its mechanism of action has not been fully elucidated. In this study, we demonstrated that MIF-deficient mice showed neither clinical signs of diarrhea and rectal bleeding nor the pathological features of colitis induced by dextran sulfate sodium (DSS)-induced colitis. The expressions of heat shock proteins were markedly up-regulated in the MIF-deficient mice in response to DSS, but not in the wild-type mice. Moreover, deletion of MIF suppressed the recruitment of inflammatory cells and the expression of chemokines in the colon of mice given DSS. In treatment study, we found that an anti-MIF autoantibody induced by DNA vaccine targeting MIF prevents mice against DSS-induced colitis. In human, granulocyte/monocyte aphresis (GMA) reduced the level of serum MIF in the patients with ulcerative colitis, suggesting that the mechanism of therapeutic effect of GMA partly is modulation of the MIF expression and its bioactivity in UC patients.
Although further study is needed to elucidate the role of MIF in colitis, the data suggest that MIF is a good target for treatment of colitis such as inflammatory bowel disease.
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