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AIM2 activa el inflamasoma y la muerte celular en respuesta al ADN citoplasmático
Teresa Fernandes-Alnemri1, Je-Wook Yu, Pinaki Datta
1Department of Biochemistry and Molecular Biology, Center for Apoptosis Research, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Nature
|January 23, 2009
Resumen
El inflamasoma ausente en el melanoma 2 (AIM2) detecta el ADN citoplasmático, activando la caspasa-1 y la piroptosis. Este descubrimiento revela AIM2
Área de la Ciencia:
- Inmunología Inmunología.
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
Sus antecedentes:
- El ADN citoplasmático de doble cadena de los huéspedes o patógenos activa los inflamatorios.
- La activación del inflammasoma conduce a la activación de la caspasa-1 y a la maduración de la pro-interleucina-1beta.
- El sensor específico para el ADN citoplasmático en la activación del inflamatorio se mantuvo sin identificar.
Objetivo del estudio:
- Para identificar la proteína sensorial responsable de la activación del inflamatorio desencadenado por el ADN citoplasmático.
- Para dilucidar el mecanismo por el cual el ADN citoplasmático activa el inflamasoma.
- Caracterizar el papel de AIM2 en la formación de inflamatorios y piroptosomas.
Principales métodos:
- Utilizó ARN corto de interferencia (siRNA) para eliminar la expresión de AIM2 en los macrófagos.
- Se evaluó la activación del inflamasoma y el piroptosoma en respuesta al ADN citoplasmático.
- AIM2 expresado en una línea celular no sensible (HEK293T) para probar la capacidad de respuesta inducida.
Principales resultados:
- Absent in melanoma 2 (AIM2) fue identificado como el sensor de ADN citoplasmático.
- El dominio de unión de oligonucleótidos/oligosacáridos (OB) de AIM2 detecta el ADN, mientras que su dominio de pirina interactúa con ASC.
- La activación de AIM2 conduce a la formación de piroptosomas ASC, la activación de caspase-1 y la muerte celular piroptótica.
Conclusiones:
- AIM2 es un componente crucial del inflamasoma que detecta el ADN citoplasmático.
- La oligomerización AIM2 es inducida por el ADN citoplasmático, iniciando el ensamblaje del inflamatorio.
- La interacción AIM2-ASC desencadena la activación de la caspasa-1 y la piroptosis, respuestas inmunes innatas cruciales.
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