The regulatory effects of cytokines on lymphatic angiogenesis.

The effects of fibroblast growth factor basic (bFGF), transforming growth factor alpha (TGF alpha), recombinant human epidermal growth factor (EGF), recombinant human tumor necrosis factor alpha (TNF alpha), and recombinant interleukin 1 alpha (IL-1 alpha) on lymphatic angiogenesis were assessed in cultured newborn bovine lymphatic endothelial cells (NBLEC). bFGF, TGF alpha, and EGF stimulated the proliferation of NBLEC in a dose-dependent manner, but the combination of either two growth factors did not show synergistic effects on NBLEC DNA synthesis. TNF alpha and IL-1 alpha suppressed the multiplication of NBLEC. Treatment with bFGF markedly increased the migration of NBLEC. The tissue plasminogen activator (t-PA) activity was enhanced by bFGF. TNF alpha also promoted NBLEC t-PA activity. These results suggest that bFGF is a major multifunctional lymphatic endothelial cell targeted cytokine, and both growth and pro-inflammatory cytokines exert differential regulatory effects on lymphatic endothelial cell proliferation, migration and t-PA activity.