Department of Medical Management and Informatics, Hokkaido Information University, Ebetsu, Hokkaido, Japan.
Ann N Y Acad Sci. 2012 Oct;1271(1):53-7. doi: 10.1111/j.1749-6632.2012.06735.x.
Macrophage migration inhibitory factor (MIF) is a unique protein that participates in inflammation, immune responses, and cell growth. An array of in vitro and in vivo experiments has demonstrated that MIF is profoundly involved in the pathogenesis of acute and chronic inflammatory disorders, such as inflammatory bowel disease (IBD). Blockade of MIF bioactivities by either neutralizing anti-MIF antibodies or antagonists prevents inflammatory cytokine cascade, which strongly suggests that an anti-MIF therapeutic strategy is feasible for treatment of IBD. Recently, we developed a new therapeutic approach for IBD by administration of antisense MIF oligonucleotides in conjugation with schizophyllan (SPG), a member of the glucan family. SPG specifically binds Dectin-1 expressed in antigen-presenting cells (APCs), and the antisense MIF/SPG complex is incorporated into the cells. In in vivo experiments of colitis models in mice, we found that intraperitoneal administration of the complex ameliorated the clinical signs of colitis and improved the histological scores. This novel therapy designed to knock down the MIF production in APCs is expected to be clinically applicable for the treatment of IBD.
巨噬细胞移动抑制因子（MIF）是一种独特的蛋白质，参与炎症、免疫反应和细胞生长。大量的体外和体内实验表明，MIF 深刻参与了急性和慢性炎症性疾病的发病机制，如炎症性肠病（IBD）。通过中和抗 MIF 抗体或拮抗剂阻断 MIF 的生物活性可以防止炎症细胞因子级联反应，这强烈表明抗 MIF 的治疗策略可用于治疗 IBD。最近，我们通过在裂褶多糖（SPG）联合下给予反义 MIF 寡核苷酸开发了一种治疗 IBD 的新方法，SPG 是葡聚糖家族的成员，它特异性地与抗原呈递细胞（APC）中表达的 Dectin-1 结合，反义 MIF/SPG 复合物被纳入细胞。在小鼠结肠炎模型的体内实验中，我们发现腹腔内给予该复合物可改善结肠炎的临床症状并改善组织学评分。这种旨在敲低 APC 中 MIF 产生的新型治疗方法有望在临床上适用于治疗 IBD。
