The role of Fas and IL-6 in experimental autoimmune encephalomyelitis

Fas和IL-6在实验性自身免疫性脑脊髓炎中的作用

• 批准号: 5374256
• 负责人: Professor Dr. Ari Waisman
• 金额: --
• 依托单位: Institut für Molekulare Medizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2004-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5374256?language=en
• 关键词: role; Fas; IL; experimental; autoimmune

Multiple sclerosis (MS), an inflammatory disease that affects nearly one million people worldwide, arises when the immune system mistakenly attacks self molecules within the white matter of the brain and spinal cord. The etiology of MS is so far unknown. Experimental autoimmune encephalomyelitis (EAE), a mouse model of brain inflammation has proven very useful for the investigation of the mechanisms that may underlie the development of MS. We want to use this model to investigate the importance of molecules involved in apoptosis and inflammation in the induction of disease. We will employ conditional gene targeting to study the involvement of two genes, which have been shown to play a major role in brain inflammation: fas and gp130, a receptor essential for response to the cytokine IL-6. Fas deficient mice were shown to be resistant to EAE induction. To test in which cell types expression of Fas contributes to brain inflammation, we will use mice in which the fas gene can be deleted in a tissue-specific manner. Similarly, because IL-6 deficient mice were shown to be resistant to EAE induction, we will use conditional gene deletion of a receptor essential for IL-6 response, gp130, to test which brain cells are important in the response to this pro-inflammatory cytokine. We use brain cell-specific Cre mice to delete the fas or the gp130 genes in oligodendrocytes, astrocytes or whole brain. The information obtained from theses experiments will shed light on molecules and cells involved in MS induction and development and allow us to design new strategies to combat this disease.

多发性硬化症（MS）是一种炎症性疾病，影响全球近100万人，当免疫系统错误地攻击大脑和脊髓白色物质中的自身分子时，就会出现这种疾病。MS的病因至今不明。实验性自身免疫性脑脊髓炎（EAE），小鼠脑炎症模型已被证明是非常有用的调查的机制，可能是MS的发展。我们想用这个模型来调查的重要性，参与细胞凋亡和炎症的诱导疾病的分子。我们将采用条件性基因靶向研究两个基因的参与，这两个基因已被证明在脑炎症中起主要作用：Fas和gp 130，一种对细胞因子IL-6反应至关重要的受体。Fas缺陷型小鼠显示对EAE诱导具有抗性。为了测试哪些细胞类型的Fas表达有助于脑炎症，我们将使用可以以组织特异性方式删除Fas基因的小鼠。类似地，由于IL-6缺陷小鼠显示对EAE诱导具有抗性，我们将使用IL-6应答所必需的受体gp 130的条件性基因缺失来测试哪些脑细胞在对这种促炎细胞因子的应答中是重要的。我们使用脑细胞特异性Cre小鼠来删除少突胶质细胞、星形胶质细胞或全脑中的fas或gp 130基因。从这些实验中获得的信息将揭示参与MS诱导和发展的分子和细胞，并使我们能够设计新的策略来对抗这种疾病。