Molecular function of macrophage migration inhibitory factor and a novel therapy for inflammatory bowel disease.
Molecular function of macrophage migration inhibitory factor and a novel therapy for inflammatory bowel disease.
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DOI：
10.1111/j.1749-6632.2012.06735.x
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发表时间：
2012-10
影响因子：
5.2
通讯作者：
Nishihira J
中科院分区：
文献类型：
--
作者：
Nishihira J
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。一系列体外和体内实验已经证明，MIF深刻地参与了急性和慢性炎症性疾病，如炎症性肠病（IBD）的发病机制。通过中和抗MIF抗体或拮抗剂阻断MIF生物活性可防止炎性细胞因子级联反应，这强烈表明抗MIF治疗策略对于治疗IBD是可行的。最近，我们开发了一种新的治疗IBD的方法，通过施用反义MIF寡核苷酸与葡聚糖家族的一个成员--葡聚糖（SPG）缀合。SPG特异性结合在抗原呈递细胞（APC）中表达的Dectin-1，并且反义MIF/SPG复合物被掺入细胞中。在小鼠结肠炎模型的体内实验中，我们发现腹膜内施用复合物改善了结肠炎的临床体征并改善了组织学评分。这种旨在敲低APC中MIF产生的新疗法预计将在临床上适用于IBD的治疗。
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.
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影响因子：
30.5
作者：
de Jong, YP;Abadia-Molina, AC;Terhorst, C
通讯作者：
Terhorst, C
影响因子：
6.3
作者：
Nohara, H;Okayama, N;Hinoda, Y
通讯作者：
Hinoda, Y
影响因子：
5
作者：
Baugh, JA;Chitnis, S;Bucala, R
通讯作者：
Bucala, R
DOI：
10.1073/pnas.56.1.72
发表时间：
1966-01-01
影响因子：
11.1
作者：
DAVID, JR
通讯作者：
DAVID, JR
影响因子：
2.3
作者：
Nishihira, J
通讯作者：
Nishihira, J