权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The role of macrophage migration inhibitory factor in inflammatory bowel disease

巨噬细胞迁移抑制因子在炎症性肠病中的作用

基本信息

批准号：
18590665
负责人：
OHKAWARA Tatsuya
金额：
$ 2.32万
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：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590665/
关键词：
Chemokine Dextran sulfate sodium-induced colitis Heat shock protein Inflammatory bowel disease Macrophaga migration inhibitory factor vaccination MIF DNAワクチン

项目摘要

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.

巨噬细胞迁移抑制因子（Macrophage migration inhibitory factor， MIF）最初在体外被鉴定为一种细胞因子衍生的活化T淋巴细胞。此外，MIF作为一种促炎细胞因子在刺激反应中从多种细胞中释放出来。MIF在炎症性疾病的发病机制中起着重要作用。在炎症性疾病中，血清和局部MIF表达显著上调。值得注意的是，在这些实验模型中，抗MIF抗体中和MIF活性可以改善炎症。另一方面，据报道，MIF在人IBD和实验性结肠炎患者的血清中升高。尽管这些结果表明MIF在结肠炎症中起关键作用，但其作用机制的分子基础尚未完全阐明。在本研究中，我们证明了mif缺陷小鼠既没有腹泻和直肠出血的临床症状，也没有葡聚糖硫酸钠（DSS）诱导结肠炎的病理特征。DSS对mif缺陷小鼠的热休克蛋白表达有显著上调，而野生型小鼠则无明显上调。此外，MIF的缺失抑制了DSS小鼠结肠中炎症细胞的募集和趋化因子的表达。在治疗研究中，我们发现以MIF为靶点的DNA疫苗诱导的抗MIF自身抗体可预防dss诱导的小鼠结肠炎。在人类中，粒细胞/单核细胞aphresis （GMA）降低了溃疡性结肠炎患者血清MIF水平，提示GMA的治疗作用机制部分是调节UC患者MIF的表达及其生物活性。虽然还需要进一步的研究来阐明MIF在结肠炎中的作用，但这些数据表明，MIF是治疗炎症性肠病等结肠炎的良好靶点。