| First Author | Ridder DA | Year | 2011 |
| Journal | J Exp Med | Volume | 208 |
| Issue | 13 | Pages | 2615-23 |
| PubMed ID | 22143887 | Mgi Jnum | J:179050 |
| Mgi Id | MGI:5301015 | Doi | 10.1084/jem.20110398 |
| Citation | Ridder DA, et al. (2011) TAK1 in brain endothelial cells mediates fever and lethargy. J Exp Med 208(13):2615-23 |
| abstractText | 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 1beta (IL-1beta)-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-1beta. 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. |
