Tumor necrosis factor type alpha, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo.
Tumor necrosis factor type alpha (TNF-alpha) inhibits endothelial cell proliferation in vitro. Basal cell growth (in the absence of exogenously added growth factor) and fibroblast growth factor (FGF)-stimulated cell proliferation are inhibited in a dose-dependent manner from 0.1 to 10 ng/ml with half-maximal inhibition occurring at 0.5-1.0 ng of TNF-alpha per ml. Bovine aortic and brain capillary endothelial and smooth muscle cells are similarly affected. TNF-alpha is a noncompetitive antagonist of FGF-stimulated cell proliferation. Its action on endothelial cells is reversible and noncytotoxic. Surprisingly, TNF-alpha does not seem to inhibit endothelial cell proliferation in vivo. In the rabbit cornea, even a high dose of TNF-alpha (10 micrograms) does not suppress angiogenesis induced by basic FGF. On the contrary, in this model system TNF-alpha stimulates neovascularization. The inflammatory response that is seen in the cornea after TNF-alpha implantation suggests that the angiogenic properties of this agent may be a consequence of leukocyte infiltration.
D000818:Animals; D001011:Aorta / Q000166:cytology; D002196:Capillaries / Q000166:cytology; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002560:Cerebrovascular Circulation; D004727:Endothelium / Q000166:cytology* / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006023:Glycoproteins / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009389:Neovascularization, Pathologic; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha
D006023:Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D005346:Fibroblast Growth Factors