TAK1 in brain endothelial cells mediates fever and lethargy.
J Exp Med
; 208(13): 2615-23, 2011 Dec 19.
Article
en En
| MEDLINE
| ID: mdl-22143887
ABSTRACT
Systemic inflammation affects the brain, resulting in fever, anorexia, lethargy, and activation of the hypothalamus-pituitary-adrenal axis. How peripheral inflammatory signals reach the brain is still a matter of debate. One possibility is that, in response to inflammatory stimuli, brain endothelial cells in proximity to the thermoregulatory centers produce cyclooxygenase 2 (COX-2) and release prostaglandin E2, causing fever and sickness behavior. We show that expression of the MAP kinase kinase kinase TAK1 in brain endothelial cells is needed for interleukin 1ß (IL-1ß)-induced COX-2 production. Exploiting the selective expression of the thyroxine transporter Slco1c1 in brain endothelial cells, we generated a mouse line allowing inducible deletion of Tak1 specifically in brain endothelium. Mice lacking the Tak1 gene in brain endothelial cells showed a blunted fever response and reduced lethargy upon intravenous injection of the endogenous pyrogen IL-1ß. In conclusion, we demonstrate that TAK1 in brain endothelial cells induces COX-2, most likely by activating p38 MAPK and c-Jun, and is necessary for fever and sickness behavior.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Encéfalo
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Quinasas Quinasa Quinasa PAM
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Células Endoteliales
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Letargia
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Fiebre
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Proteínas del Tejido Nervioso
Límite:
Animals
Idioma:
En
Revista:
J Exp Med
Año:
2011
Tipo del documento:
Article
País de afiliación:
Alemania