Investigating the physiological and biochemical role of SOCS5 in the immune system

研究 SOCS5 在免疫系统中的生理生化作用

• 批准号: nhmrc : 461232
• 负责人: A/Pr Sandra Nicholson
• 金额: $ 27.07万
• 依托单位: The Walter and Eliza Hall Institute of Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/investigating-physiological-biochemical-socs5-immune/94567
• 关键词: Investigating; physiological; biochemical; role; SOCS5

Asthma affects millions of people worldwide and is a complex inflammatory disease of the lung. Asthma manifests as recurrent episodes of wheezing, breathlessness, chest tightening, and coughing. Three key proteins called; interleukin 4 (IL-4), interleukin 13 (IL-13) and interleukin 5 (IL-5) are produced by a subset of white blood cells (T helper cells; Th2) and are thought to be responsible for the asthma response. Normally these proteins act to coordinate the body s immune defence against parasite infection. In other words, asthma is thought to arise through inappropriate IL-4 and IL-13 activity in the absence of a parasite infection. Extra IL-13 is commonly found in the lungs of asthmatics and is thought to help trigger asthma attacks. IL-13 is a validated target for drugs that could be used in the treatment of asthma. The SOCS genes were discovered in our laboratory and by genetically deleting the genes in mice we have demonstrated a critical role for SOCS1, SOCS2 and SOCS3 in regulating the immune response and the action of growth hormone. My hypothesis is that SOCS5 is an important physiologic regulator of the asthma response. This proposal will investigate the basic biochemical processes underlying the regulation of IL-4 and IL-13 action and the relationship to development of asthma and immune disease. I plan to induce asthma attacks in mice that lack the genes for SOCS4 and SOCS5. If the severity of the attacks is greater in the absence of these proteins this will indicate that SOCS4 and-or SOCS5 are important negative regulators of IL-4 and IL-13. This has the potential to open up a completely new strategy for the development of drugs that could be used in the prevention and treatment of asthma.

哮喘影响着全世界数百万人，是一种复杂的肺部炎症性疾病。哮喘表现为反复发作的喘息、呼吸困难、胸闷和咳嗽。三种关键蛋白质称为;白细胞介素4（IL-4）、白细胞介素13（IL-13）和白细胞介素5（IL-5）由一部分白色血细胞（T辅助细胞; Th 2）产生，并被认为是哮喘反应的原因。正常情况下，这些蛋白质的作用是协调人体对寄生虫感染的免疫防御。换句话说，哮喘被认为是在没有寄生虫感染的情况下通过不适当的IL-4和IL-13活性引起的。额外的IL-13通常存在于哮喘患者的肺部，被认为有助于引发哮喘发作。IL-13是可用于治疗哮喘的药物的有效靶点。SOCS基因是在我们的实验室中发现的，通过在小鼠中遗传删除这些基因，我们已经证明了SOCS 1，SOCS 2和SOCS 3在调节免疫反应和生长激素作用中的关键作用。我的假设是SOCS 5是哮喘反应的重要生理调节因子。本计划将研究IL-4和IL-13作用调节的基本生化过程以及与哮喘和免疫疾病发展的关系。我计划在缺乏SOCS 4和SOCS 5基因的小鼠中诱导哮喘发作。如果在不存在这些蛋白质的情况下发作的严重性更大，则这将表明SOCS 4和/或SOCS 5是IL-4和IL-13的重要负调节剂。这有可能为开发可用于预防和治疗哮喘的药物开辟一个全新的策略。