Involvement of TRAIL/TRAIL-R interaction in IFN-alpha-induced apoptosis of Daudi B lymphoma cells.

Interferon-alpha (IFN-alpha) exerts the anti-tumour effect on various tumours at least partly through induction of apoptosis. Apoptosis is induced by members of the tumour necrosis factor (TNF) family, including Fas (CD95) and TNF-related apoptosis-inducing ligand (TRAIL). In the present study, we examined whether the TRAIL/TRAIL-R system is involved in IFN-alpha-induced apoptosis using Daudi B lymphoma cells. IFN-alpha upregulated the expression of TRAIL within 12 h, as assessed by flow cytometry and RT-PCR, and the level increased with time until 72 h. The levels of both TRAIL-R1 and TRAIL-R2, low in Daudi cells, were enhanced by IFN-alpha. The enhanced TRAIL-R1/-R2 appeared to function as a death-inducing molecule since IFN-alpha-stimulated cells were more susceptible to TRAIL-induced cell death. The IFN-alpha-stimulated Daudi cells or their derived culture supernatants displayed cytotoxicity against TRAIL-sensitive, but not resistant lines. Moreover, the IFN-alpha-induced reduction in mitochondrial membrane potential preceding the induction of apoptosis was substantially prevented by neutralizing anti-TRAIL monoclonal antibody. Taken together, IFN-alpha-induced apoptosis appears to be mediated by the autocrine and/or paracrine loop involving TRAIL/TRAIL-R. Copyright 2001 Academic Press.