Hokkaido Information University, and Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Clin Exp Immunol. 2011 Jan;163(1):113-22. doi: 10.1111/j.1365-2249.2010.04277.x. Epub 2010 Nov 9.
Previous studies have shown that neutralization of macrophage migration inhibitory factor (MIF) by anti-MIF antibody reduces intestinal inflammation in mice. In this study we tested whether or not anti-MIF autoantibody induced by DNA vaccine targeting MIF protects mice against experimental colitis. Mice were administered a MIF-deoxyribonucleic acid (DNA) vaccine by introducing oligonucleotides encoding helper T epitope into the cDNA sequence of murine MIF by in vivo electroporation. Preventive effects of this method against dextran sulphate sodium-induced (DSS) colitis were evaluated. Mice administered with MIF-DNA vaccine raised values of autoantibody significantly. The clinical and histological findings of colitis induced by 3·0% DSS solution were ameliorated significantly in mice treated with MIF-DNA vaccine compared with saline or pCAGGS-treated mice given DSS. Myeloperoxidase activity, infiltration of F4/80-positive staining cells and the levels of proinflammatory cytokines were suppressed in the colon of MIF-DNA vaccine treated mice compared with saline or pCAGGS-treated mice exposed to DSS. Our results suggest that immunization with helper T epitope DNA-vaccine targeting MIF may be a useful approach for the treatment of colitis including inflammatory bowel diseases.
先前的研究表明，中和巨噬细胞移动抑制因子（MIF）的抗 MIF 抗体可减少小鼠的肠道炎症。在这项研究中，我们测试了针对 MIF 的 DNA 疫苗诱导的抗 MIF 自身抗体是否可以保护小鼠免受实验性结肠炎的影响。通过体内电穿孔将编码辅助 T 表位的寡核苷酸导入鼠 MIF 的 cDNA 序列中，向小鼠施用 MIF-DNA 疫苗。通过引入编码辅助 T 表位的寡核苷酸到鼠 MIF 的 cDNA 序列中，通过体内电穿孔来检测这种方法对葡聚糖硫酸钠（DSS）诱导的结肠炎的预防作用。用 MIF-DNA 疫苗治疗的小鼠中，抗 MIF 自身抗体的水平显著升高。与生理盐水或 pCAGGS 处理的给予 DSS 的小鼠相比，用 MIF-DNA 疫苗治疗的小鼠中由 3.0% DSS 溶液引起的结肠炎的临床和组织学发现得到显著改善。与生理盐水或 pCAGGS 处理的给予 DSS 的小鼠相比，MIF-DNA 疫苗处理的小鼠的髓过氧化物酶活性、F4/80 阳性染色细胞的浸润和促炎细胞因子的水平在结肠中受到抑制。我们的结果表明，针对 MIF 的辅助 T 表位 DNA 疫苗免疫可能是治疗包括炎症性肠病在内的结肠炎的一种有用方法。
