Rat Brain Vascular Distribution of Interleukin-1 Type-1 Receptor Immunoreactivity: Relationship to Patterns of Inducible Cyclooxygenase Expression by Peripheral Inflammatory Stimuli
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
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.
Cyclooxygenase-2, Endothelial cells, Immune-to-brain signaling, Interleukin-1, Prostaglandin
IdentifiersURN: urn:nbn:se:liu:diva-45769DOI: 10.1002/cne.20052ISI: 000220463400009OAI: oai:DiVA.org:liu-45769DiVA: diva2:266665