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Immune-Induced Expr...
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Hamzic, NamikLinköpings universitet,Cellbiologi,Hälsouniversitetet
(författare)
Immune-Induced Expression of Lipocalin-2 in Brain Endothelial Cells : Relationship with Interleukin-6, Cyclooxygenase-2 and the Febrile Response
- Artikel/kapitelEngelska2013
Förlag, utgivningsår, omfång ...
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2013-02-24
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Wiley,2013
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:liu-87451
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-87451URI
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https://doi.org/10.1111/jne.12000DOI
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Språk:engelska
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Sammanfattning på:engelska
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Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Interleukin (IL)-6 is critical for the febrile response to peripheral immune challenge. However, the mechanism by which IL-6 enables fever is still unknown. To characterise the IL-6-dependent fever generating pathway, we used microarray analysis to identify differentially expressed genes in the brain of lipopolysaccharide (LPS)-treated IL-6 wild-type and knockout mice. Mice lacking IL-6 displayed a two-fold lower expression of the lipocalin-2 gene (lcn2), and this difference was confirmed by real-time reverse transcriptase-polymerase chain reaction. Conversely, the induction of lipocalin-2 protein was observed in brain vascular cells following i.p. administration of recombinant IL-6, suggesting a direct relationship between IL-6 and lipocalin-2. Immunohistochemical analysis also revealed that LPS-induced lipocalin-2 is expressed by brain endothelial cells and is partly co-localised with cyclooxygenase-2 (Cox-2), the rate-limiting enzyme for the production of inflammatory induced prostaglandin E2 (PGE2), which is the key mediator of fever. The direct role of lipocalin-2 in fever was examined in LPS-challenged lipocalin-2 knockout mice. In both male and female mice, normal fever responses were observed at near-thermoneutral conditions (2930 degrees C) but when recorded at normal room temperature (1920 degrees C), the body temperature of lipocalin-2 knockout female mice displayed an attenuated fever response compared to their wild-type littermates. This difference was reflected in significantly attenuated mRNA expression of Cox-2 in the brain of lipocalin-2 knockout female mice, but not of male mice, following challenge with peripheral LPS. Our findings suggest that IL-6 influences the expression of lipocalin-2, which in turn may be involved in the control of the formation of Cox-2, and hence central PGE2-production. We have thus identified lipocalin-2 as a new factor in the pathway of inflammatory IL-6 signalling. However, the effect of lipocalin-2 on fever is small, being sex-dependent and ambient temperature-specific, and thus lipocalin-2 cannot be considered as a major mediator of the IL-6-dependent fever generating pathway.
Ämnesord och genrebeteckningar
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Interleukin-6; lipocalin-2; fever; microarray analysis
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Blomqvist, AndersLinköpings universitet,Cellbiologi,Hälsouniversitetet(Swepub:liu)andbl47
(författare)
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Nilsberth, CamillaLinköpings universitet,Cellbiologi,Hälsouniversitetet(Swepub:liu)camni68
(författare)
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Linköpings universitetCellbiologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of neuroendocrinology (Print): Wiley25:3, s. 271-2800953-81941365-2826
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