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Int Immunol ; 15(6): 741-9, 2003 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12750358

RESUMEN

Transcriptional expression of a gene or genes is absolutely required for induction of glucocorticoid-induced thymocyte apoptosis. We have previously shown that expression of T cell death-associated gene 8 (TDAG8) is quickly induced exclusively in the thymus after dexamethasone (DEX) treatment. Here, we present data that TDAG8 expression is induced prior to induction of DEX-mediated apoptosis. In contrast, TDAG8 expression in thymocytes was not induced in the process of gamma-irradiation-mediated apoptosis. TDAG8 expression accelerated only DEX-induced, but not TCR-mediated or gamma-irradiation-induced, thymocyte apoptosis in transgenic mice overexpressing TDAG8. Interestingly, these effects were specifically detected in CD4(+)CD8(+) double-positive thymocytes. Moreover, activation of caspase-3, -8 and -9 was enhanced in thymocytes of TDAG8 transgenic mice after DEX stimulation. In conclusion, TDAG8 expression is involved in glucocorticoid-induced signals to activate caspase-9, -8 and -3 for subsequent apoptosis induction in CD4(+)CD8(+) double-positive thymocytes.


Asunto(s)
Apoptosis/genética , Regulación de la Expresión Génica/inmunología , Glucocorticoides/farmacología , Receptores Acoplados a Proteínas G/genética , Linfocitos T/fisiología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Northern Blotting , Western Blotting , Caspasas/efectos de los fármacos , Caspasas/metabolismo , Células Cultivadas , Activación Enzimática/efectos de los fármacos , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Etiquetado Corte-Fin in Situ , Ratones , Ratones Transgénicos , Linfocitos T/efectos de los fármacos , Linfocitos T/patología
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