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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:e5.)
© 2008 American Heart Association, Inc.

Letters to the Editor

The Puzzling Role of TRAIL in Endothelial Cell Biology

Lee A. O’Brien; Mark A. Richardson; David T. Berg; Bruce Gerlitz; Akanksha Gupta; Brian W. Grinnell

Division of Biotechnology Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Ind

An extract of the first 250 words of the full text is provided, because this article has no abstract.

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-. 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 et al⁵ used both ELISA and flow cytometry to demonstrate that HUVECs can be induced to express TRAIL. In other cultured endothelial cells, TRAIL expression also has been documented; eg, Prat et al⁶ demonstrated that human brain endothelial cells express TRAIL, which is dramatically upregulated in response to cytokines, and Pritzker et al⁷ were able to immunoprecipitate TRAIL protein from human microvascular endothelial cells. As additional support for the physiological relevance of TRAIL expression beyond cultured cells, Spierings et al⁸ . . . [Full Text of this Article]