NF-κB functions as both a proapoptotic and antiapoptotic regulatory factor within a single cell type

Recently NF-kappa B has been shown to have both proapoptotic and antiapoptotic functions. In T cell hybridomas, both T cell activators and glucocorticoids induce apoptosis, Here we show that blockade of NF-kappa B activity, using a dominant negative I kappa B alpha, has opposite effects on these two apoptotic signals, Treatment with PMA plus ionomycin (P/I) results in the upregulation of Fas Ligand (FasL) and induction of apoptosis. Inhibition of NF-kappa B activity inhibits the P/I mediated induction of FasL mRNA and decreases the level of apoptosis in these cultures, thus establishing NF-kappa B as a proapoptotic factor in this context, Conversely, inhibition of NF-kappa B confers a tenfold increase in glucocorticoid mediated apoptosis, establishing that NF-kappa B also functions as an antiapoptotic factor. We conclude that NF-kappa B is a context-dependent apoptosis regulator. Our data suggests that NF-kappa B may function as an antiapoptotic factor in thymocytes while functioning as a proapoptotic factor in mature peripheral T cells.