Linked Life Data

20570721

Source:http://linkedlifedata.com/resource/pubmed/id/20570721

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2010-9-14
pubmed:abstractText
Fractalkine (CX(3)CL1) to fractalkine receptor (CX(3)CR1) interactions in the brain are involved in the modulation of microglial activation. Our recent findings indicate that there is microglial hyperactivity in the aged brain during an inflammatory challenge. The underlying cause of this amplified microglial response in the aged brain is unknown. Therefore, the purpose of this study was to determine the degree to which age-associated impairments of CX(3)CL1 and CX(3)CR1 in the brain contribute to exaggerated microglial activation after intraperitoneal (i.p.) injection of lipopolysaccharide (LPS). Here we show that CX(3)CL1 protein was reduced in the brain of aged (18-22 mo) BALB/c mice compared to adult (3-6 mo) controls. CX(3)CL1 protein, however, was unaltered by LPS injection. Next, CX(3)CR1 levels were determined in microglia (CD11b(+)/CD45(low)) isolated by Percoll density gradient separation at 4 and 24h after LPS injection. Flow cytometric and mRNA analyses of these microglia showed that LPS injection caused a marked decrease of CX(3)CR1 and a simultaneous increase of IL-1? at 4h after LPS injection. While surface expression of CX(3)CR1 was enhanced on microglia of adult mice by 24h, it was still significantly downregulated on a subset of microglia from aged mice. This protracted reduction of CX(3)CR1 corresponded with a delayed recovery from sickness behavior, prolonged IL-1? induction, and decreased TGFß expression in the aged brain. In the last set of studies BV2 microglia were used to determine effect of TGFß on CX(3)CR1. These results showed that TGF? enhanced CX(3)CR1 expression and attenuated the LPS-induced increase in IL-1? expression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1090-2139
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1190-201
pubmed:dateRevised
2011-10-3
pubmed:meshHeading
pubmed-meshheading:20570721-Aging, pubmed-meshheading:20570721-Animals, pubmed-meshheading:20570721-Antigens, CD11b, pubmed-meshheading:20570721-Antigens, CD45, pubmed-meshheading:20570721-Brain, pubmed-meshheading:20570721-Cell Count, pubmed-meshheading:20570721-Cells, Cultured, pubmed-meshheading:20570721-Chemokine CX3CL1, pubmed-meshheading:20570721-Down-Regulation, pubmed-meshheading:20570721-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:20570721-Flow Cytometry, pubmed-meshheading:20570721-Injections, Intraperitoneal, pubmed-meshheading:20570721-Interleukin-1beta, pubmed-meshheading:20570721-Lipopolysaccharides, pubmed-meshheading:20570721-Male, pubmed-meshheading:20570721-Mice, pubmed-meshheading:20570721-Mice, Inbred BALB C, pubmed-meshheading:20570721-Microglia, pubmed-meshheading:20570721-Polymerase Chain Reaction, pubmed-meshheading:20570721-RNA, Messenger, pubmed-meshheading:20570721-Receptors, Chemokine, pubmed-meshheading:20570721-Transforming Growth Factor beta, pubmed-meshheading:20570721-Up-Regulation
pubmed:year
2010
pubmed:articleTitle
Protracted downregulation of CX3CR1 on microglia of aged mice after lipopolysaccharide challenge.
pubmed:affiliation
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, 333 W. 10th Avenue, Columbus, OH 43210, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural