Transrepression of NF-kappaB 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 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 IkappaB induction. Moreover, glucocorticoids protected from TNF-induced apoptosis even when NF-kappaB activity was inhibited by stable or transient expression of the superrepressor IkappaB. These results demonstrate that although glucocorticoids inhibit NF-kappaB transactivation in these cells, this is not required for their protection from TNF-induced apoptosis.
Costas
M A
MA
Müller Igaz L
Holsboer
F
F
Arzt
E
E
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005347:Fibroblasts; D005938:Glucocorticoids / Q000494:pharmacology; D020672:I-kappa B Proteins; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000096:biosynthesis*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology
D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha