This competitive renewal application will continue to explore the role of IL-16 in CD4+ cell accumulation in human atopic asthma. In the previous grant period, the investigators found that IL-16 is the major lymphocyte chemoattractant released early after segmental airway antigen challenge; that the epithelium of atopic asthmatics preferentially expresses IL-16 mRNA and protein; and that the degree of epithelial expression of IL-16 correlates with the extent of CD4+ T cell accumulation and airway reactivity. They have recently observed that glucocorticoids inhibit IL-16 expression in epithelium and that IL-9, IL-13 and histamine induce IL-16 expression and secretion in human epithelial cells in vitro. The investigators propose that given IL-16's functions as a CD4+ T cell chemotactic factor, and its ability to inhibit T cell receptor mediated functions, it might function in the lung in asthma either as a pro-inflammatory or immuno-modulatory cytokine depending upon the type of local reaction. In this application, they hypothesize that airway epithelial IL-16 expression is up-regulated by Th2 cytokines and histamine and inhibited by glucocorticoids.
Their aims are to: 1) identify the IL-9, IL-13, histamine and glucocorticoid responsive regulatory elements in the IL-16 promoter; and 2) determine the factors responsible for epithelial cell secretion of IL-16.
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