Recently NF-kB 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-kB activity, using a dominant negative IkBa, 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-kB activity inhibits the P/I mediated induction of FasL mRNA and decreases the level of apoptosis in these cultures, thus establishing NF-kB as a proapoptotic factor in this context. Conversely, inhibition of NF-kB confers a tenfold increase in glucocorticoid mediated apoptosis, establishing that NF-kB also functions as an antiapoptotic factor. We conclude that NF-kB is a context-dependent apoptosis regulator. Our data suggests that NF-kB may function as an antiapoptotic factor in thymocytes while functioning as a proapoptotic factor in mature peripheral T cells.
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