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: 7959177
• 负责人: PETER R HOFFMANN
• 金额: $ 19.83万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959177
• 关键词: Acute; Affect; African American; Antibodies; Antioxidants; Asthma; CCL4 gene; CD4 Positive T Lymphocytes; Chronic; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Dietary Selenium; Dose; Exhibits; Funding; Goals; Grant; Helper-Inducer T-Lymphocyte; Histology; Human; Immune response; Institution; Intake; Investigation; Irrigation; Measures; Medical; Messenger RNA; Minority Groups; Mus; Outcomes Research; Ovalbumin; Play; Proteins; Research; Research Personnel; Resources; Role; Selenium; Serum; Source; Structure of parenchyma of lung; United States; United States National Institutes of Health; airway remodeling; asthma prevention; cytokine; design; ethnic minority population; feeding; health disparity; mouse model; research study; response; Acute; Affect; African American; Antibodies; Antioxidants; Asthma; CCL4 gene; CD4 Positive T Lymphocytes; Chronic; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Dietary Selenium; Dose; Exhibits; Funding; Goals; Grant; Helper-Inducer T-Lymphocyte; Histology; Human; Immune response; Institution; Intake; Investigation; Irrigation; Measures; Medical; Messenger RNA; Minority Groups; Mus; Outcomes Research; Ovalbumin; Play; Proteins; Research; Research Personnel; Resources; Role; Selenium; Serum; Source; Structure of parenchyma of lung; United States; United States National Institutes of Health; airway remodeling; asthma prevention; cytokine; design; ethnic minority population; feeding; health disparity; mouse model; research study; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 哮喘影响美国估计有3100万人。在患有哮喘的人中，非裔美国人和其他少数民族群体的代表性不成比例。最近的数据表明，饮食中的硒（SE）是一种有效的抗氧化剂，可能在预防哮喘中起重要作用。这项研究的长期目标是减少哮喘的人类苦难和健康差异。该项目的目的是采用小鼠模型来确定饮食硒的水平如何影响急性和慢性哮喘的发展。确定饮食中的SE和哮喘之间的关系将为人类最终的临床试验提供强大的科学框架。小鼠模型中哮喘的发展通过：肺组织切片的组织学评估；支气管灌洗以建立细胞和细胞因子谱；哮喘和气道重塑涉及各种因素的mRNA和蛋白质水平；以及支气管灌洗和血清中抗卵蛋白抗体的水平。使用这些措施，我们证明了SE摄入量和哮喘在旨在检查急性哮喘的实验中与简单的剂量反应方式无关。也就是说，我们已经表明，中SE组中的小鼠表现出最严重的哮喘，而喂养低SE或高SE的小鼠的哮喘患者则遭受不太严重的哮喘。这些结果可能有助于解释人类研究中不一致的发现，这些发现未能建立饮食中的SE和哮喘之间的关系。我们遵循了这些结果，并研究了硒通过调节T辅助细胞的增殖和分化来影响哮喘和其他免疫反应的机制。这些机械研究将提供至关重要的信息，以了解硒如何对急性和慢性哮喘的影响。