ENDOTHELIAL-CELL PROLIFERATION REGULATED BY CYTOKINES MODULATES THROMBOSPONDIN-1 SECRETION INTO THE SUBENDOTHELIUM

Endothelial cells activation and proliferation are induced by cytokine s and modulated by adhesive molecules of the extracellular matrix, In a previous study, we showed that IL-1 beta and TNF-alpha inhibited thr ombospondin-1 (TSP) secretion by human umbilical vein endothelial cell s, This work was carried on by studying the effects of other cytokines [interleukin 6 (IL-6), IL-8, basic fibroblast growth factor (bFGF), t ransforming growth factor beta (TGF-beta)] known to modulate endotheli al cell proliferation, We show here that TSP incorporation into the su bendothelial matrix is inversely proportional to cell density, Prolife rative 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 s ecretion by these cytokines is apparently due to changes in cell proli feration, Therefore, when studying the effects of cytokines on TSP sec retion, it is important to correlate the concentration of subendotheli al matrix TSP to the cell density. (C) 1997 Academic Press Limited.