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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
32
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pubmed:dateCreated |
2001-8-6
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pubmed:abstractText |
Microglia are important in the inflammatory response in Alzheimer's disease (AD). We showed previously that macrophage colony-stimulating factor receptor (M-CSFR), encoded by the c-fms protooncogene, is overexpressed on microglia surrounding amyloid beta (Abeta) deposits in the APP(V717F) mouse model for AD. The M-CSFR is also increased on microglia after experimental brain injury and in AD. To determine the relevance of these findings, we transiently expressed M-CSFR on murine BV-2 and human SV-A3 microglial cell lines using an SV40-promoted c-fms construct. M-CSFR overexpression resulted in microglial proliferation and increased expression of inducible nitric-oxide synthase, the proinflammatory cytokines interleukin-1alpha, macrophage inflammatory protein 1-alpha, and interleukin-6 and of macrophage colony-stimulating factor (M-CSF) itself. Antibody neutralization of M-CSF showed that the M-CSFR-induced proinflammatory response was dependent on M-CSF in the culture media. By using a co-culture of c-fms-transfected murine microglia and rat organotypic hippocampal slices and a species-specific real time reverse transcriptase-polymerase chain reaction assay and enzyme-linked immunosorbent assay, we showed that M-CSFR overexpression on exogenous microglia induced expression of interleukin-1alpha by the organotypic culture. These results show that increased M-CSFR expression induces microglial proliferation, cytokine expression, and a paracrine inflammatory response, suggesting that in APP(V717F) mice increased M-CSFR on microglia could be an important factor in Abeta-induced inflammatory response.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amidohydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Aminopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/L-Lactate Dehydrogenase,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Colony-Stimulating Factor,
http://linkedlifedata.com/resource/pubmed/chemical/NOS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Nos2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nos2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/peptide deformylase
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
30142-9
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pubmed:dateRevised |
2011-10-27
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pubmed:meshHeading |
pubmed-meshheading:11387343-Amidohydrolases,
pubmed-meshheading:11387343-Aminopeptidases,
pubmed-meshheading:11387343-Animals,
pubmed-meshheading:11387343-Blotting, Western,
pubmed-meshheading:11387343-Cell Division,
pubmed-meshheading:11387343-Cell Line,
pubmed-meshheading:11387343-Coculture Techniques,
pubmed-meshheading:11387343-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:11387343-Hippocampus,
pubmed-meshheading:11387343-Humans,
pubmed-meshheading:11387343-Immunohistochemistry,
pubmed-meshheading:11387343-Inflammation,
pubmed-meshheading:11387343-Interleukin-1,
pubmed-meshheading:11387343-Interleukin-6,
pubmed-meshheading:11387343-Kinetics,
pubmed-meshheading:11387343-L-Lactate Dehydrogenase,
pubmed-meshheading:11387343-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:11387343-Mice,
pubmed-meshheading:11387343-Microglia,
pubmed-meshheading:11387343-Nitric Oxide Synthase,
pubmed-meshheading:11387343-Nitric Oxide Synthase Type II,
pubmed-meshheading:11387343-Polymerase Chain Reaction,
pubmed-meshheading:11387343-Protein Binding,
pubmed-meshheading:11387343-RNA, Messenger,
pubmed-meshheading:11387343-Rats,
pubmed-meshheading:11387343-Receptor, Macrophage Colony-Stimulating Factor,
pubmed-meshheading:11387343-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:11387343-Time Factors,
pubmed-meshheading:11387343-Transfection
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pubmed:year |
2001
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pubmed:articleTitle |
Overexpression of macrophage colony-stimulating factor receptor on microglial cells induces an inflammatory response.
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pubmed:affiliation |
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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