ACT 2 PROJ 1: EFFECTS OF DIETARY SELENIUM ON THE DEVELOPMENT OF ASTHMA

第 2 步项目 1：膳食硒对哮喘发生的影响

• 批准号: 8357172
• 负责人: PETER R HOFFMANN
• 金额: $ 2.38万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-16 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357172
• 关键词: Acute; Affect; African American; Antibodies; Antioxidants; Asthma; CCL4 gene; CD4 Positive T Lymphocytes; Chronic; Clinical Trials; Data; Development; Dietary Selenium; Dose; Exhibits; Funding; Goals; Grant; Helper-Inducer T-Lymphocyte; Histology; Human; Immune response; Intake; Investigation; Irrigation; Measures; Messenger RNA; Minority Groups; Mus; National Center for Research Resources; Ovalbumin; Play; Principal Investigator; Proteins; Research; Research Infrastructure; Resources; Role; Selenium; Serum; Source; Structure of parenchyma of lung; United States; United States National Institutes of Health; airway remodeling; asthma prevention; cost; cytokine; design; ethnic minority population; feeding; health disparity; infrastructure development; mouse model; research study; response; success

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Asthma affects an estimated 31 million people in the United States. African Americans and other ethnic minority groups are disproportionately over-represented among those suffering with asthma. Recent data have suggested that dietary selenium (Se), a potent antioxidant, may play an important role in the prevention of asthma. The long-term goal of this research is to reduce the human suffering and health disparities from asthma. The objective of the project is to employ a mouse model to determine how levels of dietary selenium affect the development of acute and chronic asthma. Determining the relationship between dietary Se and asthma would provide a strong scientific framework for eventual clinical trials in humans. The development of asthma in the mouse model is evaluated by: histology of lung tissue sections; bronchiolar lavage to establish cellular and cytokine profiles; mRNA and protein levels of various factors involved in asthma and airway remodeling; and levels of anti-ovalbumin antibodies in bronchiolar lavage and serum. Using these measures, we have demonstrated that Se intake and asthma are not related in a simple dose-response manner in an experiment designed to examine acute asthma. That is, we have shown that mice in the medium-Se group exhibit the most severe asthma, while those fed low or high Se develop less severe asthma. These results may help to explain inconsistent findings in human studies that failed to establish the relationship between dietary Se and asthma. We have followed these results with investigations into the mechanisms by which selenium influences asthma and other immune response through modulating the proliferation and differentiation of T helper cells. These mechanistic studies will provide crucial information for understanding how selenium exerts its affects on both acute and chronic asthma.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 在美国，估计有3100万人患有哮喘。非裔美国人和其他少数族裔群体在哮喘患者中所占比例过高。近年来的研究表明，膳食硒作为一种有效的抗氧化剂，在预防哮喘中可能发挥重要作用。这项研究的长期目标是减少人类的痛苦和健康差异哮喘。该项目的目的是采用小鼠模型来确定膳食硒水平如何影响急性和慢性哮喘的发展。确定膳食硒和哮喘之间的关系将为最终的人类临床试验提供一个强有力的科学框架。小鼠模型中哮喘的发展通过以下方式评估：肺组织切片的组织学;细支气管灌洗以建立细胞和细胞因子谱;参与哮喘和气道重塑的各种因子的mRNA和蛋白质水平;以及细支气管灌洗和血清中抗卵清蛋白抗体的水平。使用这些措施，我们已经证明，硒的摄入量和哮喘是不相关的，在一个简单的剂量反应方式的实验设计，以检查急性哮喘。也就是说，我们已经表明，中硒组的小鼠表现出最严重的哮喘，而那些喂食低硒或高硒的小鼠则不太严重。这些结果可能有助于解释人类研究中未能建立膳食硒与哮喘之间关系的不一致结果。我们遵循这些结果，调查硒通过调节T辅助细胞的增殖和分化影响哮喘和其他免疫反应的机制。这些机制研究将为了解硒如何对急性和慢性哮喘发挥作用提供重要信息。