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

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 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。

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.