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

Abstract

We have demonstrated that interferon-α2-recombinant (IFNα) at growth inhibitory concentrations enhances the expression and signalling activity of the epidermal growth factor receptor (EGF-R) in human epidermoid carcinoma KB cells. Here we report that KB cells exposed to IFNα underwent apoptotic cell death and this effect was antagonized by EGF. We have also found that IFNα enhanced the expression of heat shock proteins (HSP) HSP-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 over-expression 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 IFNα. All these effects were neutralized by the addition of EGF to parental and JNK-1(wt) transfected KB cells exposed to IFNα. In conclusion, EGF has a protective effect on KB cells from apoptosis while antagonizing a stress response elicited by IFNα and targeted on the stress pathway terminal kinases.