Transrepression of NF-κB is not required for glucocorticoid-mediated protection of TNF-α-induced apoptosis on fibroblasts

The cellular resistance to tumor necrosis factor (TNF) of most cell types has been attributed to both a protective pathway induced by this cytokine and the preexistence of protective factors in the target cell. NF-kappaB has been postulated as one of the principal factors involved in antiapoptotic gene expression control on TNF-resistant cells. We have previously shown that glucocorticoids protect the naturally TNF-sensitive L-929 cells from apoptosis. Here we analyze the role of NF-kappaB and glucocorticoids on TNF-induced apoptosis in L-929 cells. We found that inhibition of NF-kappaB enhanced the sensitivity to TNF-induced apoptosis. Glucocorticoids inhibited NF-kappaB transactivation via I kappaB induction. Moreover, glucocorticoids protected from TNF-induced apoptosis even when NF-kappaB activity was inhibited by stable or transient expression of the superrepressor I kappaB. These results demonstrate that although glucocorticoids inhibit NF-kappaB transactivation in these cells, this is not required for their protection from TNF-induced apoptosis. (C) 2000 Elsevier Science B.V. All rights reserved.