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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
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Un papel para las mitocondrias en la activación del inflamatorio del NLRP3
Rongbin Zhou1, Amir S Yazdi, Philippe Menu
1Department of Biochemistry, Center of Immunity and Infection, University of Lausanne, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland.
Nature
|December 3, 2010
Resumen
El inflamatorio NLRP3, crucial para la inflamación, es activado por mitocondrias dañadas. El bloqueo de la autofagia causa daño mitocondrial, lo que lleva a la activación del inflamatorio NLRP3 y enfermedades inflamatorias.
Área de la Ciencia:
- Biología celular Biología celular.
- Inmunología Inmunología.
- Biología mitocondrial Biología mitocondrial
Sus antecedentes:
- El inflamasoma NLRP3 media las respuestas inflamatorias a las señales de peligro celulares.
- Su regulación implica la autofagia y las especies reactivas de oxígeno (ROS) de un orgánulo no identificado.
Objetivo del estudio:
- Para investigar el papel de las mitocondrias en la activación del inflamatorio NLRP3.
- Para identificar la fuente de ROS que regulan el inflamatorio NLRP3.
Principales métodos:
- Estudió los efectos del bloqueo de la mitofagia/autofagia en la activación del inflamatorio NLRP3.
- Investigó la localización de NLRP3 y ASC durante la activación del inflamatorio.
- Se examinó el impacto de la disfunción mitocondrial (a través de la inhibición de VDAC) en la generación de ROS y la activación del inflamatorio.
Principales resultados:
- El bloqueo de la mitofagia / autofagia condujo a la acumulación de mitocondrias dañadas que producen ROS, activando el inflamatorio NLRP3.
- NLRP3 y ASC translocados al espacio perinuclear, co-localizando con ER y las mitocondrias tras la activación.
- La inhibición de la actividad mitocondrial suprimió la generación de ROS y la activación del inflamatorio NLRP3.
Conclusiones:
- El inflamatorio NLRP3 detecta la disfunción mitocondrial.
- El daño mitocondrial contribuye a las enfermedades inflamatorias.
- Este estudio identifica a las mitocondrias como la fuente de los ROS que regulan la actividad inflamatoria del NLRP3.
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