Reduced severity of experimental autoimmune encephalomyelitis in GMF-deficient mice
Reduced severity of experimental autoimmune encephalomyelitis in GMF-deficient mice
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DOI：
10.1007/s11064-006-9220-x
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发表时间：
2007-01-01
影响因子：
4.4
通讯作者：
Lim, Ramon
中科院分区：
文献类型：
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作者：
Zaheer, Asgar;Zaheer, Smita;Lim, Ramon
神经胶质成熟因子 (GMF) 是一种高度保守的大脑特异性蛋白质，在我们的实验室中进行了分离、测序和克隆。星形胶质细胞中 GMF 的过度表达诱导粒细胞巨噬细胞集落刺激因子 (GM-CSF) 的产生和分泌，随后小胶质细胞的免疫激活，包括主要组织相容性复合体蛋白、IL-1β 和 MIP-1β 在内的几种促炎基因的表达，所有这些都与实验性自身免疫性脑脊髓炎 (EAE)（多发性硬化症的动物模型）的发展有关。基于 GMF 激活小胶质细胞并诱导成熟的促炎介质（包括 GM-CSF）的能力，我们假设 GMF 参与炎症性疾病 EAE 的发病机制。在本次研究中，我们使用 GMF 缺陷小鼠研究了 GMF 的作用以及缺乏 GMF 如何影响 EAE 疾病。我们的结果表明，GMF 缺陷小鼠中 EAE 的发病率显着降低、发病延迟并减轻了严重程度，并支持了 GMF 在疾病发病机制中发挥重要作用的假设。
Glia maturation factor (GMF), a highly conserved brain-specific protein, isolated, sequenced and cloned in our laboratory. Overexpression of GMF in astrocytes induces the production and secretion of granulocyte-macrophage-colony stimulating factor (GM-CSF), and subsequent immune activation of microglia, expression of several proinflammatory genes including major histocompatibility complex proteins, IL-1 beta, and MIP-1 beta, all associated with the development of experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. Based on GMF's ability to activate microglia and induce well-established proinflammatory mediators, including GM-CSF, we hypothesize that GMF is involved in the pathogenesis of inflammatory disease EAE. In this present investigation, using GMF-deficient mice, we study the role of GMF and how the lack of GMF affects the EAE disease. Our results show a significant decrease in incidence, delay in onset, and reduced severity of EAE in GMF-deficient mice, and support the hypothesis that GMF plays a major role in the pathogenesis of disease.