Gamma-interferon (IFN-gamma) augments apoptotic response to mistletoe lectin-II via upregulation of Fas/Fas L expression and caspase activation in human myeloid U937 cells

Mistletoe lectin-II, a major composition of Korean mistletoe (Viscum album coloratum), is known as a potent apoptosis inducer. The previous re search has demonstrated that Korean mistletoe lectin-II induces apoptosis via c-Ju n N terminal kinase (JNK) activation in human myeloid U937 cells. The purpo se of this research is to prove the synergistic action of mistletoe lectin- II and interferon-gamma (IFN-gamma) in the apoptotic cytotoxicity of U937. When U937 cells were treated with mistletoe lectin-II after being different iated by IFN-gamma, the proteolytic activity of caspase-3 and 9 was markedl y elevated and that of caspase-8 was prolonged for 18 hr. The activation of caspase-3-like protease requires the earlier cleavage of poly(ADP-ribose) polymerase(PARP). Caspase-1 was, however, not activated during the resting phase and nor in IFN-gamma -differentiated U937 cells. Western blot analysi s revealed that, in IFN-gamma -differentiated U937 cells, the expression of Fas (CD95/APO-1) & Fas ligand(FasL) increases the apoptotic sensitivity ag ainst Mistletoe lectin-II. Fas (CD95/APO-1) Br FasL were not significantly induced solely by mistletoe lectin-II. Furthermore the activity of JNK1 in U937 cells was also markedly increased with IFN-gamma -differentiation, com pared to that of the control. These results suggest that the IFN-gamma -dif ferentiation of U937 cells increases the susceptibility to mistletoe lectin -II-induced apoptosis.