title: Rat brain vascular distribution of interleukin-1 type-1 receptor immunoreactivity: relationship to patterns of inducible cyclooxygenase expression by peripheral inflammatory stimuli.
abstract: Interleukin-1 beta (IL-1 beta) 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-1 beta 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-1 beta 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-1 beta- 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 kappa B mRNA upon IL-1 beta stimulation, and colocalized with peripheral IL-1 beta- 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.
authors.affiliation: Laboratoire de Neurobiologie Intégrative, Centre National de la Recherche Scientifique FRE 2723/Institut National de la Recherche Agronomique UR 1244, Institut François Magendie, 33077 Bordeaux, France. konsman@bordeaux.inserm.fr
authors.forename: Jan Pieter
authors.initials: JP
authors.lastname: Konsman
authors.forename: Stephan
authors.initials: S
authors.lastname: Vigues
authors.forename: Ludmila
authors.initials: L
authors.lastname: Mackerlova
authors.forename: Adrian
authors.initials: A
authors.lastname: Bristow
authors.forename: Anders
authors.initials: A
authors.lastname: Blomqvist
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000276:immunology / Q000473:pathology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism* / Q000633:toxicity; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000032:analysis / Q000096:biosynthesis*; D053573:Receptors, Interleukin-1 Type I
chemical_list: D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D011451:Prostaglandin-Endoperoxide Synthases