Interferon-alpha induces apoptosis in human KB cells through a stress-dependent mitogen activated protein kinase pathway that is antagonized by epidermal growth factor

We have demonstrated that interferon-alpha 2-recombinant (IFN alpha) at gro wth inhibitory concentrations enhances the expression and signalling activi ty of the epidermal growth factor receptor (EGF-R) in human epidermoid carc inoma KB cells, Here we report that KB cells exposed to IFN alpha underwent apoptotic cell death and this effect was antagonized by EGF, We have also found that IFN alpha enhanced the expression of heat shock proteins (HSP) H SP-70, HSP-90 and HSP-27 and activated the NH2-terminal Jun kinase-1 (JNK-1 ) and p38 mitogen activated protein kinase, the target enzymes of a stress- dependent intracellular transduction pathway. Moreover, the overexpression of the wild-type JNK-1, obtained through plasmid transfection of KB cells, induced apoptosis which was potentiated by the exposure of wild-type JNK-1 (JNK-1(wt))-transfected cells to IFN alpha. All these effects were neutrali zed by the addition of EGF to parental and JNK-1(wt)-transfected KB cells e xposed to IFN alpha. In conclusion, EGF has a protective effect on KB cells from apoptosis while antagonizing a stress response elicited by IFN alpha and targeted on the stress pathway terminal kinases.