| Immune-induced expression of lipocalin-2 in brain endothelial cells: relationship to interleukin-6, cyclooxygenase-2 and the febrile response. | |
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MedLine Citation:
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PMID: 23046379 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Interleukin-6 (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 characterize 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 knock-out mice. Mice lacking IL-6 displayed two-times lower expression of the lipocalin-2 gene (lcn2), and this difference was confirmed by real-time RT-PCR. Conversely, 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-localized with cyclooxygenase-2 (Cox-2), the rate limiting enzyme for the production of inflammatory induced prostaglandin E(2) (PGE(2) ), the key mediator of fever. The direct role of lipocalin-2 in fever was examined in LPS-challenged lipocalin-2 knock-out mice. In both male and female mice, normal fever responses were observed at near-thermoneutral conditions (29-30°C), but when recorded at normal room temperature (19-20°C), the body temperature of lipocalin-2 knock-out female mice displayed an attenuated and delayed fever response compared with their wild type littermates. This difference was reflected in significantly attenuated mRNA expression of Cox-2 in the brain of lipocalin-2 knock-out 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 the central PGE(2) -production. We have thus identified lipocalin-2 as a new factor in the pathway of inflammatory IL-6 signaling. However, the effect of lipocalin-2 on fever is small, being sex-dependent and ambient temperature-specific, and thus lipocalin-2 cannot be considered a major mediator of the IL-6-dependent fever generating pathway. © 2012 The Authors. Journal of Neuroendocrinology © 2012 British Society for Neuroendocrinology. |
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Authors:
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Namik Hamzic; Anders Blomqvist; Camilla Nilsberth |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-10-10 |
Journal Detail:
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Title: Journal of neuroendocrinology Volume: - ISSN: 1365-2826 ISO Abbreviation: J. Neuroendocrinol. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8913461 Medline TA: J Neuroendocrinol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 The Authors. Journal of Neuroendocrinology © 2012 British Society for Neuroendocrinology. |
Affiliation:
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Linköping University, Faculty of Health Sciences, Department of Clinical and Experimental Medicine, Division of Cell Biology, SE-581 85, Linköping, Sweden. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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