Mechanisms of resistance of normal cells to TRAIL induced apoptosis vary between different cell types

Resistance of normal cells to tumour necrosis factor related apoptosis indu cing ligand (TRAIL) induced apoptosis is believed to be mediated by express ion of two decoy receptors. Here we show that the expression and localisati on of TRAIL receptors (TRAIL-Rs) vary between different cells and that resi stance to TRAIL is mediated by different mechanisms. The decoy receptor, TR AIL-R3, appeared important in protection of endothelial cells, whereas lack of surface death receptor expression and as yet unknown intracellular inhi bitor(s) of apoptosis downstream of caspase-3 may play a major role in prot ection of melanocytes and fibroblasts from TRAIL induced apoptosis, respect ively. Differential subcellular location of decoy receptors may be an impor tant determinant of their effectiveness in different types of normal cells. (C) 2000 Federation of European Biochemical Societies. Published by Elsevi er Science B.V. All rights reserved.