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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| Hauptverfasser: | , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
December 05 2011
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| In: |
Journal of experimental medicine
Year: 2011, Jahrgang: 208, Heft: 13, Pages: 2615-2623 |
| ISSN: | 1540-9538 |
| DOI: | 10.1084/jem.20110398 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1084/jem.20110398
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| Verfasserangaben: | Dirk A. Ridder, Ming-Fei Lang, Sergei Salinin, Jan-Peter Röderer, Marcel Struss, Christiane Maser-Gluth, and Markus Schwaninger |
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| 520 | |a 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. | ||
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