This project is focused on the regulation of interleukin-4 receptor (IL-4R) expression on hematopoietic progenitor cells. Using the murine myeloid leukemia Ml line and mature, bone marrow-derived macrophages, neither of which express IL-4R, we have previously characterized the ability of IL-6 and/or interferon-gamma (IFN-gamma) to induce the expression of IL-4R. We are now continuing with these studies to determine the mechanism of this induction. To this end, we have obtained the putative promoter sequence for the IL-4 receptor gene and are trying to transfect hematopoietic cells with these constructs to localize the promoter region responsible for IL-6 and IFN-gamma sensitivity. In a parallel series of studies, we have determined that although both IFN-gamma and IL-6 are individually capable of inducing IL-4R, they have an antagonistic effect on each other when combined. We are currently pursuing studies to characterize and understand the nature of this antagonistic effect.