INTERLEUKIN-1 AND REGULATION OF HEMATOPOIESIS

    Project: Research project

    Description

    The long term objective of this application is to characterize the
    molecular mechanisms by which IL-1 enhances the stability and function of
    cytokine mRNA in stromal cells of the human hematopoietic microenvironment.
    During the past funding period, we have determined that IL-1 governs the
    expression of multiple hematopoietic growth factor genes in endothelial
    cells and fibroblasts, in large part, by stabilizing gene transcripts.
    Specifically, we have found that GM-CSF, G-CSF, IL-1beta, and IL-6 mRNAs
    are stabilized in IL-1 stimulated diploid fibroblasts and human vascular
    endothelial cells. Using a cell-free method that faithfully reproduces the
    effect of IL-1 on mRNA stability, we have noted that an IL-1-induced RNase
    inhibitory factor can be reconstituted by reaction mixtures containing
    polysome-bound proteins and cytosolic co-factors. Using these same
    mixtures, we have also demonstrated that IL-1 induces mRNA binding proteins
    to bind to specific regions of the GM-CSF mRNA molecule known to
    destabilize the transcript. These methods, combined with promoter/reporter
    analysis in intact cells provide us with the tools necessary to achieve our
    specific aims; (1) to purify and characterize the biological activity of
    cellular factors activated by IL-1 that stabilize cytokine mRNA and (2) to
    identify specific attributes (sequences and/or secondary structural
    features) of cytokine mRNA chains that permit them to be stabilized in
    response to IL-1.
    StatusFinished
    Effective start/end date1/1/8412/31/96

    Funding

    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health: $237,493.00
    • National Institutes of Health
    • National Institutes of Health: $176,973.00
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health: $212,703.00
    • National Institutes of Health
    • National Institutes of Health

    Fingerprint

    Hematopoiesis
    Monokines
    Interleukin-1
    Fibroblasts
    Stromal Cells
    Gene Expression
    Phagocytes
    Bone Marrow
    Granulocyte-Macrophage Progenitor Cells
    Intercellular Signaling Peptides and Proteins
    Nuclear Family
    Interleukin-4
    Messenger RNA
    Leukemia
    Endothelial Cells
    Macrophages
    Genes
    Monocytes
    Granulocyte-Macrophage Colony-Stimulating Factor
    T-Lymphocytes

    ASJC

    • Medicine(all)