Ma. Costas et al., Transrepression of NF-kappa B is not required for glucocorticoid-mediated protection of TNF-alpha-induced apoptosis on fibroblasts, BBA-MOL CEL, 1499(1-2), 2000, pp. 122-129
Citations number
33
Categorie Soggetti
Cell & Developmental Biology
Journal title
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
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.