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TAK1 in brain endothelial cells mediates fever and lethargy

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...

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Bibliographic Details
Main Authors: Ridder, Dirk (Author) , Lang, Ming-Fei (Author) , Salinin, Sergei (Author) , Röderer, Jan-Peter (Author) , Struss, Marcel (Author) , Maser-Gluth, Christiane (Author) , Schwaninger, Markus (Author)
Format: Article (Journal)
Language:English
Published: December 05 2011
In: Journal of experimental medicine
Year: 2011, Volume: 208, Issue: 13, Pages: 2615-2623
ISSN:1540-9538
DOI:10.1084/jem.20110398
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1084/jem.20110398
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Author Notes:Dirk A. Ridder, Ming-Fei Lang, Sergei Salinin, Jan-Peter Röderer, Marcel Struss, Christiane Maser-Gluth, and Markus Schwaninger
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Summary: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 1β (IL-1β)-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-1β. 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.
Item Description:Gesehen am 15.09.2022
Physical Description:Online Resource
ISSN:1540-9538
DOI:10.1084/jem.20110398

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