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Rat Brain Vascular Distribution of Interleukin-1 Type-1 Receptor Immunoreactivity: Relationship to Patterns of Inducible Cyclooxygenase Expression by Peripheral Inflammatory Stimuli
Laboratoire de Neurobiologie Intégrative, Centre National de la Recherche Scientifique FRE 2723 / Institut National de la Recherche Agronomique UR 1244, Institut François Magendie, Bordeaux, France.
Division of Endocrinology, National Institute for Biological Standards and Control, Herts, United Kingdom.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Division of Endocrinology, National Institute for Biological Standards and Control, Herts, United Kingdom.
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2004 (English)In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 472, no 1, 113-129 p.Article in journal (Refereed) Published
Abstract [en]

Interleukin-1ß (IL-1ß) is thought to act on the brain to induce fever, neuroendocrine activation, and behavioral changes during disease through induction of prostaglandins at the blood-brain barrier (BBB). However, despite the fact that IL-1ß induces the prostaglandin-synthesizing enzyme cyclooxygenase-2 (COX-2) in brain vascular cells, no study has established the presence of IL-1 receptor type 1 (IL-1R1) protein in these cells. Furthermore, although COX inhibitors attenuate expression of the activation marker c-Fos in the preoptic and paraventricular hypothalamus after administration of IL-1ß or bacterial lipopolysaccharide (LPS), they do not alter c-Fos induction in other structures known to express prostaglandin receptors. The present study thus sought to establish whether IL-1R1 protein is present and functional in the rat cerebral vasculature. In addition, the distribution of IL-1R1 protein was compared to IL-1ß- and LPS-induced COX-2 expression. IL-1R1-immunoreactive perivascular cells were mostly found in choroid plexus and meninges. IL-1R1-immunoreactive vessels were seen throughout the brain, but concentrated in the preoptic area, subfornical organ, supraoptic hypothalamus, and to a lesser extent in the paraventricular hypothalamus, cortex, nucleus of the solitary tract, and ventrolateral medulla. Vascular IL-1R1-ir was associated with an endothelial cell marker, not found in arterioles, and corresponded to the induction patterns of phosphorylated c-Jun and inhibitory-factor kappaB mRNA upon IL-1ß stimulation, and colocalized with peripheral IL-1ß- or LPS-induced COX-2 expression. These observations indicate that functional IL-1R1s are expressed in endothelial cells of brain venules and suggest that vascular IL-1R1 distribution is an important factor determining BBB prostaglandin-dependent activation of brain structures during infection. © 2004 Wiley-Liss, Inc.

Place, publisher, year, edition, pages
John Wiley & Sons, 2004. Vol. 472, no 1, 113-129 p.
Keyword [en]
Cyclooxygenase-2, Endothelial cells, Immune-to-brain signaling, Interleukin-1, Prostaglandin
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URN: urn:nbn:se:liu:diva-45769DOI: 10.1002/cne.20052ISI: 000220463400009OAI: diva2:266665
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2015-03-27Bibliographically approved

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Mackerlova, LudmilaBlomqvist, Anders
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Cell BiologyFaculty of Health Sciences
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