Involvement of trail/trail-R interaction in IFN-alpha-induced apoptosis ofdaudi B lymphoma cells

Interferon-alpha (IFN-alpha) exerts the anti-tumour effect on various tumou rs at least partly through induction of apoptosis, Apoptosis is induced by members of the tumour necrosis factor (TNF) family, including Fas (CD95) an d TNF-related apoptosis-inducing ligand (TRAIL), In the present study, we e xamined whether the TRAIL/TRAIL-R system is involved in LFN-alpha -induced apoptosis using Daudi B lymphoma cells, IFN-alpha upregulated the expressio n of TRAIL within 12 h, as assessed by flow cytometry and RT-PCR, and the l evel increased with time until 72 h, The levels of both TRAIL-R1 and TRAIL- R2, low in Daudi cells, were enhanced by LFN-alpha, The enhanced TRAIL-R1/- R2 appeared to function as a death-inducing molecule since IFN-alpha -stimu lated cells were more susceptible to TRAIL-induced cell death, The IFN-alph a -stimulated Daudi cells or their derived culture supernatants displayed c ytotoxicity 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 ant i-TRAIL monoclonal antibody. Taken together, IFN-alpha -induced apoptosis a ppears to be mediated by the autocrine and/or paracrine loop involving TRAI L/TRAIL-R. (C) 2001 Academic Press.