Modulation of Hemopoietic Factor Production in Relation to Endothelial Cell Aging by Interleukin-1 Induction

Abstract

In this study, we examined the modulation of hemopoietic factor production by human umbilical vein endothelial cells in relation to aging and the cell cycle under conditions of interleukin-1 (IL-1) induction and noninduction. Under conditions of IL-1 noninduction, messenger RNA expression levels of macrophage colony-stimulating factor (M-CSF) were three times higher in non-S-phase cells of young cultures than those in S-phase cells. Expression levels decreased in non-S-phase cells of old culture and approached levels similar to that of S-phase cells. The expression of neither E-selectin nor erythropoietin (Epo) was detected in cells from the noninduced state. The expression of granulocyte colony-stimulating factor (G-CSF) was not affected by either cellular aging or the cell cycle; however, the amount of product secreted increased significantly in old cells, suggesting that G-CSF production is under posttranscriptional regulation. Under conditions of IL-1 induction G-CSF and M-CSF expression levels were enhanced in both young and old cells. Expression of Epo was not detected whereas E-selectin was induced. Significant M-CSF product was detected in young cells but not in old cells, whereas G-CSF product increased dramatically in both types of cells. The modulation of these factors is discussed in relation to the maintenance of neutrophil concentration, differentiation, and maturation of leukocytes and their possible effect on atherosclerosis.