The Puzzling Role of TRAIL in Endothelial Cell Biology

In Response: The letter by Secchiero and Zauli regarding our study on TRAIL suppression via the Egr-1/Erk1/2 pathway by activated protein C (APC)1 comments positively on the mechanistic data, but questions the pathophysiological role of TRAIL on endothelial cells, largely based on their inability to detect TRAIL in cultured human umbilical vein endothelial cells (HUVECs). In our article, we used HUVECs as a model system to study the signaling response to APC, with TRAIL as a response gene after activation by tumor necrosis factor (TNF)-alpha. The expression of TRAIL by HUVECs and its regulation by inflammatory mediators is well described in the literature. As we originally cited, Fu et al2 demonstrated that TRAIL is highly expressed in cultured HUVECs and regulated by overexpression of Egr-1. Viemann and colleagues3 demonstrated TRAIL expression in HUVECs, which could be upregulated 4-fold by TNF-α. Larghero et al4 studied the effect of lipoic acid on HUVEC function and demonstrated an induction of TRAIL expression and suggested a relationship to in vivo antiangiogenic activity. Warke …