Transrepression of NF-kappa B is not required for glucocorticoid-mediated protection of TNF-alpha-induced apoptosis on fibroblasts

The cellular resistance to tumor necrosis factor (TNF) of most cell types h as been attributed to both a protective pathway induced by this cytokine an d the preexistence of protective factors in the target cell. NF-kappaB has been postulated as one of the principal factors involved in antiapoptotic g ene expression control on TNF-resistant cells. We have previously shown tha t glucocorticoids protect the naturally TNF-sensitive L-929 cells from apop tosis. Here we analyze the role of NF-kappaB and glucocorticoids on TNF-ind uced apoptosis in L-929 cells. We found that inhibition of NF-kappaB enhanc ed the sensitivity to TNF-induced apoptosis. Glucocorticoids inhibited NF-k appaB transactivation via I kappaB induction. Moreover, glucocorticoids pro tected from TNF-induced apoptosis even when NF-kappaB activity was inhibite d by stable or transient expression of the superrepressor I kappaB. These r esults demonstrate that although glucocorticoids inhibit NF-kappaB transact ivation in these cells, this is not required for their protection from TNF- induced apoptosis. (C) 2000 Elsevier Science B.V. All rights reserved.