PMID- 16882009
OWN - NLM
STAT- MEDLINE
DCOM- 20060905
LR  - 20220309
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 24
IP  - 1
DP  - 2006 Jul
TI  - Brain cytokine synthesis induced by an intraparenchymal injection of LPS is 
      reduced in MCP-1-deficient mice prior to leucocyte recruitment.
PG  - 77-86
AB  - We have previously shown that ischaemic lesions are smaller in monocyte 
      chemoattractant protein-1-deficient (MCP-1(-/-)) mice than in wild-type (wt) 
      controls. In addition to its role as a monocyte chemoattractant, monocyte 
      chemoattractant protein-1 (MCP-1) has been proposed to contribute to lesion 
      progression after focal ischaemia by driving local cytokine synthesis by resident 
      glia. To investigate this hypothesis we injected lipopolysaccharide (LPS) into 
      the brain parenchyma of MCP-1(-/-) mice and compared the resulting inflammatory 
      response and production of proinflammatory cytokines to those in wt mice. 
      Microglial and astrocyte morphological activation was the same in the two 
      strains, but MCP-1(-/-) mice showed significantly lower levels of proinflammatory 
      cytokine synthesis; interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha 
      (TNF-alpha) levels were up to 50% lower than in wt controls after 6 h. This 
      reduced synthesis of proinflammatory cytokines occurred well before leucocyte 
      recruitment to the central nervous system (CNS) is observed in this model of 
      acute inflammation and thus cannot be attributed to lower numbers of recruited 
      monocytes at the site of injury. We propose that MCP-1 contributes to acute CNS 
      inflammation by pleiotropic mechanisms. In addition to being a potent 
      chemoattractant for monocytes, we provide evidence here that MCP-1 can modify the 
      responsiveness of CNS glia to acute inflammatory stimuli prior to leucocyte 
      recruitment, thereby acting as a priming stimulus for cytokine synthesis in cells 
      such as microglia.
FAU - Rankine, E L
AU  - Rankine EL
AD  - Nurin Ltd, School of Biological Sciences, University of Southampton, Southampton, 
      SO16 7PX, UK.
FAU - Hughes, P M
AU  - Hughes PM
FAU - Botham, M S
AU  - Botham MS
FAU - Perry, V H
AU  - Perry VH
FAU - Felton, L M
AU  - Felton LM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Astrocytes/pathology
MH  - Brain/*drug effects/metabolism/pathology
MH  - Cell Count
MH  - Chemokine CCL2/genetics/*physiology
MH  - Cytokines/*biosynthesis
MH  - Encephalitis/chemically induced/metabolism/pathology
MH  - *Lipopolysaccharides/administration & dosage
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microglia/pathology
EDAT- 2006/08/03 09:00
MHDA- 2006/09/06 09:00
CRDT- 2006/08/03 09:00
PHST- 2006/08/03 09:00 [pubmed]
PHST- 2006/09/06 09:00 [medline]
PHST- 2006/08/03 09:00 [entrez]
AID - EJN4891 [pii]
AID - 10.1111/j.1460-9568.2006.04891.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2006 Jul;24(1):77-86. doi: 10.1111/j.1460-9568.2006.04891.x.