THE REGULATORY EFFECTS OF CYTOKINES ON LYMPHATIC ANGIOGENESIS

The effects of fibroblast growth factor basic (bFGF), transforming gro wth factor alpha (TGF alpha), recombinant human epidermal growth facto r (EGF), recombinant human tumor necrosis factor alpha (TNF alpha), an d recombinant interleukin 1 alpha (IL-1 alpha) on lymphatic angiogenes is were assessed in cultured newborn bovine lymphatic endothelial cell s (NBLEC). bFGF, TGF alpha, and EGF stimulated the proliferation of NB LEC in a dose-dependent manner, but the combination of either two grow th factors did not show synergistic effects on NBLEC DNA synthesis. TN F alpha and IL-1 alpha suppressed the multiplication of NBLEC. Treatme nt with bFGF markedly increased the migration of NBLEC. The tissue pla sminogen activator (t-PA) activity was enhanced by bFGF. TNF alpha als o promoted NBLEC t-PA activity. These results suggest that bFGF is a m ajor multifunctional lymphatic endothelial cell targeted cytokine, and both growth and pro-inflammatory cytokines exert differential regulat ory effects on lymphatic endothelial cell proliferation, migration and t-PA activity.