TRAIL is a protein that is considered a promising cancer therapeutic because it can kill tumor cells and can synergize with conventional chemotherapeutic agents to destroy tumor cells. However, controversy surrounds whether or not TRAIL affects nontumor cells, in particular cells of the liver -- which are known as hepatocytes. Now, Thomas Brunner and colleagues from the University of Bern in Switzerland show that although TRAIL alone does not kill mouse hepatocytes in vitro, it does enhance both in vitro and in vivo hepatocyte cell death induced by signaling through another protein on the surface of hepatocytes known as Fas. This study, which is published in the September issue of the Journal of Clinical Investigation, indicates that TRAIL can enhance hepatocyte cell death, and therefore liver damage, initiated by signaling through Fas. This has important clinical implications because cells that are able to trigger signaling through Fas are present in the liver, especially during inflammation, making liver damage a potential risk of TRAIL-based therapeutics.
TITLE: TRAIL receptor–mediated JNK activation and Bim phosphorylation critically regulate Fas-mediated liver damage and lethality
University of Bern, Bern, Switzerland.
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