Functional manipulation of dendritic cells by photoswitchable generation of intracellular reactive oxygen species.
ACS Chem Biol
; 10(3): 757-65, 2015 Mar 20.
Article
em En
| MEDLINE
| ID: mdl-25458073
ABSTRACT
Reactive oxygen species (ROS) play an important role in cellular signaling as second messengers. However, studying the role of ROS in physiological redox signaling has been hampered by technical difficulties in controlling their generation within cells. Here, we utilize two inert components, a photosensitizer and light, to finely manipulate the generation of intracellular ROS and examine their specific role in activating dendritic cells (DCs). Photoswitchable generation of intracellular ROS rapidly induced cytosolic mobilization of Ca(2+), differential activation of mitogen-activated protein kinases, and nuclear translocation of NF-κB. Moreover, a transient intracellular ROS surge could activate immature DCs to mature and potently enhance migration in vitro and in vivo. Finally, we observed that intracellular ROS-stimulated DCs enhanced antigen specific T-cell responses in vitro and in vivo, which led to delayed tumor growth and prolonged survival of tumor-bearing mice when immunized with a specific tumor antigen. Therefore, a transient intracellular ROS surge alone, if properly manipulated, can cause immature DCs to differentiate into a motile state and mature forms that are sufficient to initiate adaptive T cell responses in vivo.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Regulação Neoplásica da Expressão Gênica
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Espécies Reativas de Oxigênio
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Neoplasias do Colo
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Imunidade Adaptativa
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Antígenos de Neoplasias
Limite:
Animals
Idioma:
En
Revista:
ACS Chem Biol
Ano de publicação:
2015
Tipo de documento:
Article