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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2004-9-24
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pubmed:abstractText |
Recent studies have shown that the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) possess antiinflammatory and immunomodulatory properties, distinct from their action of lowering serum lipid levels. Moreover, results of epidemiological studies suggest that long-term use of statins is associated with a decreased risk for Alzheimer's disease (AD). Interestingly, lovastatin (one of the most commonly used anticholesterol drugs) treatment of vascular-derived cells has been reported to antagonize activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, and it is well known that the JAK/STAT pathway plays a central role in interferon-gamma (IFN-gamma)-induced microglial CD40 expression. We and others have previously reported that microglial CD40 expression is significantly induced by IFN-gamma and amyloid-beta (Abeta) peptide. Moreover, it has been shown that CD40 signaling is critically involved in microglia-related immune responses in the CNS. In this study, we examined the putative role of lovastatin in modulation of CD40 expression and its signaling in cultured microglia. RT-PCR, Western immunoblotting, and flow cytometry data show that lovastatin suppresses IFN-gamma-induced CD40 expression. Additionally, lovastatin markedly inhibits IFN-gamma-induced phosphorylation of JAK/STAT1. Furthermore, lovastatin is able to suppress microglial tumor necrosis factor-alpha, interleukin (IL)-beta1 and IL-6 production promoted either by IFN-gamma or by Abeta peptide challenge in the presence of CD40 cross-linking. To characterize further lovastatin's effect on microglial function, we examined microglial phagocytic capability following CD40 cross-linking. Data reveal that lovastatin markedly attenuates CD40-mediated inhibition of microglial phagocytosis of Abeta. These results provide an insight into the mechanism of the beneficial effects of lovastatin in neurodegenerative disorders, particularly Alzheimer's disease.
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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/Amyloid beta-Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD40,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Jak1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Jak2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Lovastatin,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Stat1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/amyloid beta-protein (1-42)
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0360-4012
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pubmed:author |
pubmed-author:FernandezFranciscoF,
pubmed-author:FreemanMelissaM,
pubmed-author:GardnerJ MeeksJM,
pubmed-author:MorganDavidD,
pubmed-author:MoriTakashiT,
pubmed-author:RuiL XLX,
pubmed-author:SanNanN,
pubmed-author:ShytleDoug RDR,
pubmed-author:TownsendKirk PKP,
pubmed-author:YinBeiB,
pubmed-author:ZengJinJ
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pubmed:copyrightInfo |
Copyright 2004 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
78
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
167-76
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15378516-Amyloid beta-Peptides,
pubmed-meshheading:15378516-Animals,
pubmed-meshheading:15378516-Antigens, CD40,
pubmed-meshheading:15378516-Cells, Cultured,
pubmed-meshheading:15378516-Cytokines,
pubmed-meshheading:15378516-DNA-Binding Proteins,
pubmed-meshheading:15378516-Interferon-gamma,
pubmed-meshheading:15378516-Janus Kinase 1,
pubmed-meshheading:15378516-Janus Kinase 2,
pubmed-meshheading:15378516-Lovastatin,
pubmed-meshheading:15378516-Mice,
pubmed-meshheading:15378516-Mice, Inbred BALB C,
pubmed-meshheading:15378516-Microglia,
pubmed-meshheading:15378516-Peptide Fragments,
pubmed-meshheading:15378516-Phagocytosis,
pubmed-meshheading:15378516-Protein-Tyrosine Kinases,
pubmed-meshheading:15378516-Proto-Oncogene Proteins,
pubmed-meshheading:15378516-STAT1 Transcription Factor,
pubmed-meshheading:15378516-Signal Transduction,
pubmed-meshheading:15378516-Trans-Activators
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pubmed:year |
2004
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pubmed:articleTitle |
Lovastatin modulation of microglial activation via suppression of functional CD40 expression.
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pubmed:affiliation |
Neuroimmunology Laboratory, Department of Psychiatry and Behavioral Medicine, University of South Florida College of Medicine, Tampa, Florida 33613, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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