Characterization of signaling pathways leading to Fas expression induced by TNF-alpha: pivotal role of NF-kappaB.
FASEB J
; 19(3): 473-5, 2005 Mar.
Article
em En
| MEDLINE
| ID: mdl-15601669
TNF-alpha is known to induce a strong up-regulation of Fas expression in mouse Sertoli cell cultures, leading to their apoptosis triggered by effector FasL-bearing cells. These data suggest that increased Fas expression on the cell surface might be a key event in the pathogenesis of autoimmune orchitis, by inducing a leakage of the blood-tubular barrier as a consequence of Sertoli cell apoptosis. In the present paper, we have investigated the signal transduction mechanisms involved in the regulation of Fas expression induced by TNF-alpha in mouse Sertoli cells. We studied the role of the transcription factor NF-kappaB and of MAPKs in regulating Fas expression. By using Sertoli cells transfected with a NF-kappaB Luc reporter gene, we proved that TNF-alpha activates the IkappaB/NF-kappaB system. Moreover, the use of the proteasome inhibitor lactacystin led us to demonstrate that NF-kappaB is required for TNF-alpha mediated Fas expression. By using specific inhibitors for each MAPK, we confirmed the pivotal role of the IkappaB/NF-kappaB system by demonstrating that ERKs, p38, and JNK are not involved in Fas up-regulation by TNF-alpha. The comprehension of these pathways could be relevant to the knowledge of the pathogenesis of autoimmune disorders in immune privileged districts of the body.
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Regulação da Expressão Gênica
/
NF-kappa B
/
Fator de Necrose Tumoral alfa
/
Receptor fas
Limite:
Animals
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article