Deletion of Prostaglandin E-2 Synthesizing Enzymes in Brain Endothelial Cells Attenuates Inflammatory Fever
2014 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 34, no 35, 11684-11690 p.Article in journal (Refereed) Published
Fever is a hallmark of inflammatory and infectious diseases. The febrile response is triggered by prostaglandin E-2 synthesis mediated by induced expression of the enzymes cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase 1 (mPGES-1). The cellular source for pyrogenic PGE(2) remains a subject of debate; several hypotheses have been forwarded, including immune cells in the periphery and in the brain, as well as the brain endothelium. Here we generated mice with selective deletion of COX-2 and mPGES1 in brain endothelial cells. These mice displayed strongly attenuated febrile responses to peripheral immune challenge. In contrast, inflammation-induced hypoactivity was unaffected, demonstrating the physiological selectivity of the response to the targeted gene deletions. These findings demonstrate that PGE(2) synthesis in brain endothelial cells is critical for inflammation-induced fever.
Place, publisher, year, edition, pages
Society for Neuroscience , 2014. Vol. 34, no 35, 11684-11690 p.
COX-2; endothelium; fever; mPGES-1; PGE(2); prostaglandin
Cell and Molecular Biology Neurosciences
IdentifiersURN: urn:nbn:se:liu:diva-111281DOI: 10.1523/JNEUROSCI.1838-14.2014ISI: 000341314900017PubMedID: 25164664OAI: oai:DiVA.org:liu-111281DiVA: diva2:755384
Funding Agencies|Swedish Medical Research Council; Swedish Cancer Foundation; European Research Council; Knut and Alice Wallenberg Foundation; Swedish Brain foundation; County Council of stergotland; Wenner-Gren Fellowship2014-10-142014-10-142015-11-06