In vitro biosynthesis of leukemia inhibitory factor/human interleukin for DA cells by human endothelial cells : differential regulation by interleukin-1α and glucocorticoids

Endothelial cell (EC) may represent a major source of cytokines in the bone marrow. In this study we have examined the production and the regulation of the production of leukemia inhibitory factor/human interleukin for DA cells (LIF/HILDA) by EC. Human umbilical vein endothelial cells (HUVEC) were chosen as a working model as they are a well known source of cytokines. These cells secrete LIF/HILDA (90 pg/mL/10(6) cells/48 h) in basal conditions. This secretion is profoundly altered by interleukin-1 alpha (IL-1 alpha). Secretion of LIF/HILDA is increased threefold on stimulation with IL-1 alpha at a concentration of 100 IU/mL. The secreted protein is bioactive as demonstrated by its proliferative effects on DA1a cells. Modulation of the production of LIF/HILDA by glucocorticoids (GC) was also examined. In striking contrast to what was observed for IL-1 alpha, the synthetic GC dexamethasone (DXM) at a concentration of 10(-6) mol/L consistently inhibited the basal secretion of LIF/HILDA by an average of threefold and suppressed the IL-1 alpha-induced increase of the secretion of this cytokine by HUVEC. In an effort to extend results obtained with HUVEC to the bone marrow endothelium, we have also examined the production of LIF/HILDA by human bone marrow endothelial cells (HBMEC). Our study shows that HBMEC are quantitatively a very important source of this cytokine (above 7.25 ng/mL/10(6) cells/48 h) suggesting that they are a major source of LIF/HILDA in the bone marrow. Again, IL-1 alpha proved to be a very potent stimulus for the secretion of LIF/HILDA and synthetic GC such as DXM when used at a concentration of 10(-6) mol/L inhibited by an average of threefold the basal secretion of LIF/HILDA and had suppressive effect on the IL-1 alpha-induced increase of this secretion. The downregulation of LIF/HILDA production in the bone marrow by GC may be important to understand the effects of GC on hematopoiesis.