CYTOKINE RESCUE FROM GLUCOCORTICOID-INDUCED APOPTOSIS IN T-CELLS IS MEDIATED THROUGH INHIBITION OF I-KAPPA-B-ALPHA

We previously reported that dexamethasone (DEX), a synthetic glucocort icoid, causes apoptosis in mature Th cell lines, and that this inducti on of cell death is prevented by specific cytokines, namely, by IL-2 i n Th1 cells and by IL-4 in Th2 cells. We now show that this differenti al rescue by specific cytokines in Th cells correlates with the level of I kappa B alpha that is regulated by DEX and cytokines. In both cel l types the cellular levels of I kappa B alpha mRNA and protein were e valuated by DEX treatment. Interestingly, the DEX-mediated I kappa B a lpha induction was completely inhibited by IL-2, but not IL-4, in Th1 cells, while the reverse profile was seen in Th2 cells. In both cell t ypes, the cytokine that inhibits the induction of I kappa B alpha by D EX, also rescues these cells from DEX-induced apoptosis, although the rescue cytokine is different in Th1 and Th2 cells. Our results imply t hat T cells need to maintain a certain level of NF-kappa B transcripti onal activity in order to survive; up-or down-regulation of nuclear NF kappa B through modulation of I kappa B alpha expression by cytokines or DEX may lead to cell survival or cell death, respectively. (C) 199 7 Elsevier Science Ltd. All rights reserved.