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
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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.
(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.
PMID: 15024756 [Indexed for MEDLINE]