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Polyamines play a critical role in the control of the innate immune response in the mouse central nervous system

Soulet, Denis LU and Rivest, Serge (2003) In Journal of Cell Biology 162(2). p.257-268
Abstract
The present work investigated whether polyamines play a role in the control of the innate immune response in the brain. The first evidence that these molecules may be involved in such a process was based on the robust increase in the expression of the first and rate-limiting enzyme of biosynthesis of polyamines during immune stimuli. Indeed, systemic lipopolysaccharide (LPS) administration increased ornithine decarboxylase (ODC) mRNA and protein within neurons and microglia across the mouse central nervous system (CNS). This treatment was also associated with a robust and transient transcriptional activation of genes encoding pro-inflammatory cytokines and toll-like receptor 2 (TLR2) in microglial cells. The endotoxin increased the... (More)
The present work investigated whether polyamines play a role in the control of the innate immune response in the brain. The first evidence that these molecules may be involved in such a process was based on the robust increase in the expression of the first and rate-limiting enzyme of biosynthesis of polyamines during immune stimuli. Indeed, systemic lipopolysaccharide (LPS) administration increased ornithine decarboxylase (ODC) mRNA and protein within neurons and microglia across the mouse central nervous system (CNS). This treatment was also associated with a robust and transient transcriptional activation of genes encoding pro-inflammatory cytokines and toll-like receptor 2 (TLR2) in microglial cells. The endotoxin increased the cerebral activity of ODC, which was abolished by a suicide inhibitor of ODC. The decrease in putrescine levels largely prevented the ability of LPS to trigger tumor necrosis factor alpha and TLR2 gene transcription in the mouse brain. In contrast, expression of both transcripts was clearly exacerbated in response to intracerebral spermine infusion. Finally, inhibition of polyamine synthesis abolished neurodegeneration and increased the survival rate of mice exposed to a model of severe innate immune reaction in the CNS. Thus, polyamines have a major impact on the neuronal integrity and cerebral homeostasis during immune insults. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Cell Biology
volume
162
issue
2
pages
257 - 268
publisher
Rockefeller University Press
external identifiers
  • pmid:12860970
  • scopus:0042171801
ISSN
0021-9525
DOI
10.1083/jcb.200301097
language
English
LU publication?
yes
id
4a5c0fc1-7837-40aa-9d80-a47839725276 (old id 1128086)
date added to LUP
2008-06-04 11:12:36
date last changed
2018-10-21 03:42:42
@article{4a5c0fc1-7837-40aa-9d80-a47839725276,
  abstract     = {The present work investigated whether polyamines play a role in the control of the innate immune response in the brain. The first evidence that these molecules may be involved in such a process was based on the robust increase in the expression of the first and rate-limiting enzyme of biosynthesis of polyamines during immune stimuli. Indeed, systemic lipopolysaccharide (LPS) administration increased ornithine decarboxylase (ODC) mRNA and protein within neurons and microglia across the mouse central nervous system (CNS). This treatment was also associated with a robust and transient transcriptional activation of genes encoding pro-inflammatory cytokines and toll-like receptor 2 (TLR2) in microglial cells. The endotoxin increased the cerebral activity of ODC, which was abolished by a suicide inhibitor of ODC. The decrease in putrescine levels largely prevented the ability of LPS to trigger tumor necrosis factor alpha and TLR2 gene transcription in the mouse brain. In contrast, expression of both transcripts was clearly exacerbated in response to intracerebral spermine infusion. Finally, inhibition of polyamine synthesis abolished neurodegeneration and increased the survival rate of mice exposed to a model of severe innate immune reaction in the CNS. Thus, polyamines have a major impact on the neuronal integrity and cerebral homeostasis during immune insults.},
  author       = {Soulet, Denis and Rivest, Serge},
  issn         = {0021-9525},
  language     = {eng},
  number       = {2},
  pages        = {257--268},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Cell Biology},
  title        = {Polyamines play a critical role in the control of the innate immune response in the mouse central nervous system},
  url          = {http://dx.doi.org/10.1083/jcb.200301097},
  volume       = {162},
  year         = {2003},
}