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

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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 thatmice 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.