Tumor necrosis factor-alpha upregulates angiopoietin-2 in human umbilical vein endothelial cells

The angiopoietin-Tie2 system is an important regulator of vasculogenesis and vascular integrity. Angiopoietin-2 (Ang2) disrupts blood vessel formation in the developing embryo by antagonizing the effects of angiopoietin-1 (Ang1) on the Tie2 receptor. In this study, we examined the effect of a well-known proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), on Ang2 expression in human umbilical vein endothelial cells. Reverse transcriptase-polymerase chain reaction and Northern blot analyses indicated that TNF-alpha induced Ang2 mRNA expression in a time- and dose-dependent manner. Western blot analyses revealed that TNF-alpha treatment increased cellular Ang2 protein. TNF-alpha induced less Ang2 mRNA expression in the presence of nuclear factor-kappaB (NF-kappaB) inhibitor. These results suggest that TNF-alpha-induced inflammatory angiogenesis might be facilitated by the induction of Ang2.