VASCULAR ENDOTHELIAL-CELLS AND HEMATOPOIESIS - REGULATION OF GENE-EXPRESSION IN HUMAN VASCULAR ENDOTHELIAL-CELLS

Vascular endothelial cells do not constitutively produce significant quantities of hematopoietic growth factors, interleukins, or adhesion molecules, but they can be induced to do so by a variety of stimuli including the inductive cytokines, interleukin-1 (IL-1), and tumor necrosis factor-alpha, as well as phorbol esters, bacterial proteins, endotoxin, certain viruses, and modified low-density lipoproteins. Recently, some groups have begun to investigate the molecular mechanism by which expression of these genes is regulated. Because induced expression of the gene products is always prefaced by an increase in mRNA the focus of attention has been largely upon the mechanisms involved in the process of transcript accumulation. Certain inducing agents drive transcription of these genes, others may induce both transcription and transcript stability. In the case of the inducing factor IL-1, it was recently demonstrated that accumulation of G-CSF, GM-CSF, and interleukin-1-beta mRNAs induced in vascular endothelial cells occurs as a result of transcript stabilization. Based on preliminary studies in a cell-free system, it is proposed that the inductive capacity of interleukin-1 results, at least in part, from its capacity to activate cytoplasmic inhibitors of selective ribonucleases and hypothesize that this may be a mechanism that has been conserved throughout evolution. Because other inducing agents also incite IL-1 gene expression, transcript stabilization may be a common ingredient of most inductive stimuli.