Document Detail


Cerebral microglia recruit monocytes into the brain in response to tumor necrosis factoralpha signaling during peripheral organ inflammation.
MedLine Citation:
PMID:  19228962     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In inflammatory diseases occurring outside the CNS, communication between the periphery and the brain via humoral and/or neural routes results in central neural changes and associated behavioral alterations. We have recently identified another immune-to-CNS communication pathway in the setting of organ-centered peripheral inflammation: namely, the entrance of immune cells into the brain. In our current study, using a mouse model of inflammatory liver injury, we have confirmed the significant infiltration of activated monocytes into the brain in mice with hepatic inflammation and have defined the mechanism that mediates this trafficking of monocytes. Specifically, we show that in the presence of hepatic inflammation, mice demonstrate elevated cerebral monocyte chemoattractant protein (MCP)-1 levels, as well as increased numbers of circulating CCR2-expressing monocytes. Cerebral recruitment of monocytes was abolished in inflamed mice that lacked MCP-1/CCL2 or CCR2. Furthermore, in mice with hepatic inflammation, microglia were activated and produced MCP-1/CCL2 before cerebral monocyte infiltration. Moreover, peripheral tumor necrosis factor (TNF)alpha signaling was required to stimulate microglia to produce MCP-1/CCL2. TNFalpha signaling via TNF receptor 1 (TNFR1) is required for these observed effects since in TNFR1 deficient mice with hepatic inflammation, microglial expression of MCP-1/CCL2 and cerebral monocyte recruitment were both markedly inhibited, whereas there was no inhibition in TNFR2 deficient mice. Our results identify the existence of a novel immune-to-CNS communication pathway occurring in the setting of peripheral organ-centered inflammation which may have specific implications for the development of alterations in cerebral neurotransmission commonly encountered in numerous inflammatory diseases occurring outside the CNS.
Authors:
Charlotte D'Mello; Tai Le; Mark G Swain
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  29     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-20     Completed Date:  2009-04-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2089-102     Citation Subset:  IM    
Affiliation:
Immunology Research Group, Department of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Proliferation
Cerebral Cortex / cytology,  immunology*,  physiopathology
Chemokine CCL2 / metabolism
Chemokines / metabolism
Chemotaxis, Leukocyte / genetics,  immunology
Cytokines / metabolism
Hepatitis / immunology,  physiopathology
Illness Behavior / physiology
Inflammation / immunology*,  physiopathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Microglia / immunology*
Monocytes / immunology*
Receptors, CCR2 / metabolism
Receptors, Tumor Necrosis Factor, Type I / genetics,  metabolism
Signal Transduction / genetics,  immunology
Tumor Necrosis Factor-alpha / metabolism*
Chemical
Reg. No./Substance:
0/Ccl2 protein, mouse; 0/Ccr2 protein, mouse; 0/Chemokine CCL2; 0/Chemokines; 0/Cytokines; 0/Receptors, CCR2; 0/Receptors, Tumor Necrosis Factor, Type I; 0/Tnfrsf1a protein, mouse; 0/Tumor Necrosis Factor-alpha

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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