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

• Autores: Costas, M.A.; Müller Igaz, L.; Holsboer, F.; Arzt, E.
• Año de publicación: 2000
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Biochim. Biophys. Acta Mol. Cell Res. 2000;1499(1-2):122-129
• Materia: Apoptosis; Glucocorticoid; Glucocorticoid receptor; Nuclear factor-κB; Tumor necrosis factor; beta galactosidase; dexamethasone; glucocorticoid; glucocorticoid receptor; I kappa B; immunoglobulin enhancer binding protein; luciferase; messenger RNA; tumor necrosis factor alpha; tumor necrosis factor alpha receptor; DNA binding protein; glucocorticoid; glucocorticoid receptor; I kappa B; immunoglobulin enhancer binding protein; NF kappaB inhibitor alpha; NF-kappaB inhibitor alpha; tumor necrosis factor alpha; animal cell; apoptosis; article; cell protection; controlled study; cytotoxicity; fibroblast; gene expression regulation; gene repression; mouse; nonhuman; priority journal; protein expression; suppressor cell; target cell destruction; transactivation; animal; biosynthesis; cell line; drug antagonism; genetic transfection; metabolism; Animals; Apoptosis; Cell Line; DNA-Binding Proteins; Fibroblasts; Glucocorticoids; I-kappa B Proteins; Mice; NF-kappa B; Receptors, Glucocorticoid; Transfection; Tumor Necrosis Factor-alpha
• Institución: Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales

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-κB 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-κB and glucocorticoids on TNF-induced apoptosis in L-929 cells. We found that inhibition of NF-κB enhanced the sensitivity to TNF-induced apoptosis. Glucocorticoids inhibited NF-κB transactivation via IκB induction. Moreover, glucocorticoids protected from TNF-induced apoptosis even when NF-κB activity was inhibited by stable or transient expression of the superrepressor IκB. These results demonstrate that although glucocorticoids inhibit NF-κB transactivation in these cells, this is not required for their protection from TNF-induced apoptosis. (C) 2000 Elsevier Science B.V.
Fil:Costas, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Müller Igaz, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.