Endothelial cell proliferation regulated by cytokines modulates thrombospondin-1 secretion into the subendothelium.

Endothelial cells activation and proliferation are induced by cytokines and modulated by adhesive molecules of the extracellular matrix. In a previous study, we showed that IL-1beta and TNF-alpha inhibited thrombospondin-1 (TSP) secretion by human umbilical vein endothelial cells. This work was carried on by studying the effects of other cytokines [interleukin 6 (IL-6), IL-8, basic fibroblast growth factor (bFGF), transforming growth factor beta (TGF-beta)] known to modulate endothelial cell proliferation. We show here that TSP incorporation into the subendothelial matrix is inversely proportional to cell density. Proliferative cytokines such as IL-6 and bFGF inhibit TSP secretion, whereas the anti-proliferative TGF-beta enhances it. IL-8 has no effect either on cell proliferation or TSP secretion. Thus, the modulation of TSP secretion by these cytokines is apparently due to changes in cell proliferation. Therefore, when studying the effects of cytokines on TSP secretion, it is important to correlate the concentration of subendothelial matrix TSP to the cell density.