Bh. Lin et al., NF-kappa B functions as both a proapoptotic and antiapoptotic regulatory factor within a single cell type, CELL DEAT D, 6(6), 1999, pp. 570-582
Recently NF-kappa B has been shown to have both proapoptotic and antiapopto
tic functions. In T cell hybridomas, both T cell activators and glucocortic
oids induce apoptosis, Here we show that blockade of NF-kappa B activity, u
sing 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 d
ecreases the level of apoptosis in these cultures, thus establishing NF-kap
pa B as a proapoptotic factor in this context, Conversely, inhibition of NF
-kappa B confers a tenfold increase in glucocorticoid mediated apoptosis, e
stablishing that NF-kappa B also functions as an antiapoptotic factor. We c
onclude that NF-kappa B is a context-dependent apoptosis regulator. Our dat
a suggests that NF-kappa B may function as an antiapoptotic factor in thymo
cytes while functioning as a proapoptotic factor in mature peripheral T cel
ls.