INTERLEUKIN-1 AND REGULATION OF HEMATOPOIESIS

  • Bagby, Grover (PI)

Project: Research project

Project Details

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

ASJC

  • Medicine(all)

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.