TNF-alpha in vivo stimulates apoptosis in fibroblasts through caspase-8 activation and modulates the expression of pro-apoptotic genes.
J Cell Physiol
; 201(3): 341-8, 2004 Dec.
Article
en En
| MEDLINE
| ID: mdl-15389560
ABSTRACT
Apoptosis of matrix producing cells is common among many inflammatory diseases. The goal of the present study was to examine the apoptotic effects of tumor necrosis factor-alpha (TNF-alpha) on fibroblastic cells in vivo and to investigate the role of different caspases in this process. This was accomplished in vivo by subcutaneous injection of TNF-alpha in mice. The direct effects of TNF-alpha on fibroblast apoptosis were studied in vitro with normal diploid human fibroblasts. The results indicate that TNF-alpha in vivo induces apoptosis of fibroblasts. By RNase protection assay, we demonstrated that TNF-alpha stimulates expression of 12 apoptotic genes. Fluorometric studies demonstrated that TNF-alpha in vivo predominantly increased caspase-8 and -3 activity and by use of specific inhibitors, the activation of caspase-3 was shown to be initiated by caspase-8 with only a minor contribution from caspase-9. Thus, TNF-alpha acts to modulate the expression of many genes that favors apoptosis of fibroblastic cells, which is dependent mostly upon signaling through caspase-8.
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Base de datos:
MEDLINE
Asunto principal:
Regulación de la Expresión Génica
/
Factor de Necrosis Tumoral alfa
/
Apoptosis
/
Caspasas
Idioma:
En
Revista:
J Cell Physiol
Año:
2004
Tipo del documento:
Article