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- Eskilsson, Anna (författare)
Immune-Induced Fever Is Mediated by IL-6 Receptors on Brain Endothelial Cells Coupled to STAT3-Dependent Induction of Brain Endothelial Prostaglandin Synthesis
- E-artikel/E-kapitelEngelska2014
Förlag, utgivningsår, omfång ...
- Society for Neuroscience2014
Nummerbeteckningar
- LIBRIS-ID:20158804
- http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-113199uri
- urn:nbn:se:liu:diva-113199urn
- 10.1523/JNEUROSCI.3520-14.2014doi
Kompletterande språkuppgifter
- Språk:engelska
Ingår i deldatabas
Anmärkningar
- <p>Funding Agencies|Swedish Medical Research Council; Swedish Cancer Foundation; European Research Council; Knut and Alice Wallenberg Foundation; Swedish Brain foundation; County CouncilO Ostergotland</p>
- Published
- gratis
- The cytokine IL-6, which is released upon peripheral immune challenge, is critical for the febrile response, but the mechanism by which IL-6 is pyrogenic has remained obscure. Herewegenerated mice with deletion of themembranebound IL-6 receptor alpha (IL-6R alpha) onneural cells, on peripheral nerves, on fine sensory afferent fibers, and on brain endothelial cells, respectively, and examined its role for the febrile response to peripherally injected lipopolysaccharide. We show that IL-6R alpha on neural cells, peripheral nerves, and fine sensory afferents are dispensable for the lipopolysaccharide-induced fever, whereas IL-6R alpha in the brain endothelium plays an important role. Hence deletion of IL-6R alpha on brain endothelial cells strongly attenuated the febrile response, and also led to reduced induction of the prostaglandin synthesizing enzyme Cox-2 in the hypothalamus, the temperature-regulating center in the brain, as well as reduced expression of SOCS3, suggesting involvement of the STAT signaling pathway. Furthermore, deletion of STAT3 in the brain endothelium also resulted in attenuated fever. These data show that IL-6, when endogenously released during systemic inflammation, is pyrogenic by binding to IL-6R alpha on brain endothelial cells to induce prostaglandin synthesis in these cells, probably in concerted action with other peripherally released cytokines.
Ämnesord och genrebeteckningar
- Medical and Health Sciences hsv
- Clinical Medicine hsv
- Medicin och hälsovetenskap hsv
- Klinisk medicin hsv
- blood-brain barrier; cell-specific gene deletions; fever; interleukin-6; prostaglandins; STAT3
Biuppslag (personer, institutioner, konferenser, titlar ...)
- Mirrasekhian, Elahe (författare)
- Dufour, Sylvie (författare)
- Schwaninger, Markus (författare)
- Engblom, David (författare)
- Blomqvist, Anders (författare)
- Linköpings universitetInstitutionen för klinisk och experimentell medicin347333 (utgivare)
- Linköpings universitetHälsouniversitetet (utgivare)
Sammanhörande titlar
- Del av/supplement till:channel record
- Ingår i:VärdpublikationJournal of Neuroscience34:48, 15957-159610270-6474
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