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The Journal of Neuroscience, December 15, 1999, 19(24):10923-10930
An Essential Role of Interleukin-1 in Mediating NF- B
Activity and COX-2 Transcription in Cells of the Blood-Brain Barrier
in Response to a Systemic and Localized Inflammation But Not During
Endotoxemia
Nathalie
Laflamme,
Steve
Lacroix, and
Serge
Rivest
Laboratory of Molecular Endocrinology, Centre de Recherche de
l'Université Laval Research Center and Department of Anatomy and
Physiology, Laval University, Québec, Canada G1V 4G2
When released into the bloodstream, proinflammatory cytokines have
the ability to trigger the transcription of different genes in cells of
the blood-brain barrier (BBB), including members of the nuclear factor
kappa B (NF- B) family and cyclooxygenase-2 (COX-2), the limiting
enzyme for the formation of prostaglandins (PGs). The present study
investigated the possibility that interleukin-1 (IL-1 ) plays an
essential role in these events during a systemic inflammatory response.
Both wild-type and IL-1 -deficient mice were killed at different
times after two different immunogenic stimuli, i.e.,
intraperitoneal lipopolysaccharide (LPS) injection and
intramuscular turpentine injection, used here as a model of systemic
localized inflammatory insult. The inhibitory factor B (I B ,
index of NF- B activity) and COX-2 transcripts were detected
throughout the brain by means of in situ hybridization. Systemic LPS injection caused a strong and rapid expression of I B
in endothelial cells lining the BBB of large and small blood vessels
and thereafter within parenchymal microglia across the brain. This
treatment also provoked a transient expression of COX-2 along cells of
the vascular system, and the expression pattern and intensity of the
signal for both transcripts were essentially the same in wild-type and
IL-1 -deficient animals. In contrast, the induction of these genes
that was quite selective to the cells of the BBB in response to
intramuscularly turpentine insult was completely abolished in
IL-1 -deficient mice. Indeed, a late and prolonged expression of
I B and COX-2 mRNAs was found along the cerebral blood vessels in
response to the sterile and localized inflammation in wild-type mice,
whereas such induction was absent in the brain of IL-1 -deficient
animals. These results indicate that IL-1 has an obligatory role in
the activation of NF- B molecules and PGs within endothelial cells of
the BBB in an experimental model of intramuscularly turpentine-induced
inflammation but not during endotoxemia.
Key words:
blood vessels; circumventricular organs; endothelial
cells; in situ hybridization histochemistry; inflammation; interleukin-1 -deficient mice; immunocytochemistry; lipopolysaccharide; proinflammatory cytokines; microglia; macrophages; septic shock; transcription factor
Copyright © 1999 Society for Neuroscience 0270-6474/99/192410923-08$05.00/0
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