Rat brain vascular distribution of interleukin-1 type-1 receptor immunoreactivity: relationship to patterns of inducible cyclooxygenase expression by peripheral inflammatory stimuli.
J. Comp. Neurol.. 2004-01-01; 472(1): 113-129
DOI: 10.1002/cne.20052
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1. J Comp Neurol. 2004 Apr 19;472(1):113-29.
Rat brain vascular distribution of interleukin-1 type-1 receptor
immunoreactivity: relationship to patterns of inducible cyclooxygenase expression
by peripheral inflammatory stimuli.
Konsman JP(1), Vigues S, Mackerlova L, Bristow A, Blomqvist A.
Author information:
(1)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.
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.
Copyright 2004 Wiley-Liss, Inc.
DOI: 10.1002/cne.20052
PMID: 15024756 [Indexed for MEDLINE]