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-κB has been postulated as one of the principal factors involved in antiapoptotic gene...
| Autores: | , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2000 |
| País: | Argentina |
| Institución: | Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales |
| Repositorio: | Biblioteca Digital (UBA-FCEN) |
| Idioma: | inglés |
| OAI Identifier: | paperaa:paper_01674889_v1499_n1-2_p122_Costas |
| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_01674889_v1499_n1-2_p122_Costas |
| Access Level: | acceso abierto |
| Palabra clave: | 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 NF kappaB inhibitor alpha NF-kappaB inhibitor 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 Cell Line DNA-Binding Proteins Fibroblasts Glucocorticoids I-kappa B Proteins Mice NF-kappa B Receptors, Glucocorticoid Transfection Tumor Necrosis Factor-alpha |
| Sumario: | 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. |
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