Source:http://linkedlifedata.com/resource/pubmed/id/19175796
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1 Suppl
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| pubmed:dateCreated |
2009-9-10
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| pubmed:abstractText |
The inflammatory effects of glycogen synthase kinase-3 (GSK-3) have been identified; however, the potential mechanism is still controversial. In this study, we investigated the effects of GSK-3-mediated interleukin-10 (IL-10) inhibition on lipopolysaccharide (LPS)-induced inflammation. Treatment with GSK-3 inhibitor significantly blocked LPS-induced nitric oxide (NO) production as well as inducible NO synthase (iNOS) expression in BV2 murine microglial cells and primary rat microglia-enriched cultures. Using an antibody array and enzyme-linked immunosorbent assay, we found that GSK-3-inhibitor treatment blocked LPS-induced upregulation of regulated on activation normal T-cell expressed and secreted (RANTES) and increased IL-10 expression. The time kinetics and dose-response relations were confirmed. Reverse transcription-polymerase chain reaction showed changes on the messenger RNA level as well. Inhibiting GSK-3 using short-interference RNA, and transfecting cells with dominant-negative GSK-3beta, blocked LPS-elicited NO and RANTES expression but increased IL-10 expression. In contrast, GSK-3beta overexpression upregulated NO and RANTES but downregulated IL-10 in LPS-stimulated cells. Treating cells with anti-IL-10 neutralizing antibodies to prevent GSK-3 from downregulating NO and RANTES showed that the anti-inflammatory effects are, at least in part, IL-10-dependent. The involvement of Akt, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase and nuclear factor-kappaB that positively regulated IL-10 was demonstrated. Furthermore, inhibiting GSK-3 increased the nuclear translocation of transcription factors, that all important for IL-10 expression, including CCAAT/enhancer-binding protein beat (C/EBPbeta), C/EBPdelta, cAMP response binding element protein and NF-kappaB. Taken together, these findings reveal that LPS induces iNOS/NO biosynthesis and RANTES production through a mechanism involving GSK-3-mediated IL-10 downregulation.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Neutralizing,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL5,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
1365-2567
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| pubmed:author |
pubmed-author:BazoutováMM,
pubmed-author:ChenChia-LingCL,
pubmed-author:ChenPo-SeePS,
pubmed-author:HongJau-ShyongJS,
pubmed-author:HuangWei-ChingWC,
pubmed-author:LiQianQ,
pubmed-author:LinChiou-FengCF,
pubmed-author:LinYee-ShinYS,
pubmed-author:LuPei-JungPJ,
pubmed-author:TsaiCheng-ChiehCC,
pubmed-author:TsengHsiang-ChiHC
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| pubmed:issnType |
Electronic
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| pubmed:volume |
128
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
e275-86
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| pubmed:dateRevised |
2010-9-2
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| pubmed:meshHeading |
pubmed-meshheading:19175796-Animals,
pubmed-meshheading:19175796-Antibodies, Neutralizing,
pubmed-meshheading:19175796-Cell Line,
pubmed-meshheading:19175796-Chemokine CCL5,
pubmed-meshheading:19175796-Down-Regulation,
pubmed-meshheading:19175796-Glycogen Synthase Kinase 3,
pubmed-meshheading:19175796-Inflammation,
pubmed-meshheading:19175796-Interleukin-10,
pubmed-meshheading:19175796-Lipopolysaccharides,
pubmed-meshheading:19175796-Mice,
pubmed-meshheading:19175796-Microglia,
pubmed-meshheading:19175796-NF-kappa B,
pubmed-meshheading:19175796-Nitric Oxide,
pubmed-meshheading:19175796-Nitric Oxide Synthase Type II,
pubmed-meshheading:19175796-Protein Kinase Inhibitors,
pubmed-meshheading:19175796-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:19175796-RNA, Small Interfering,
pubmed-meshheading:19175796-Rats,
pubmed-meshheading:19175796-Up-Regulation,
pubmed-meshheading:19175796-p38 Mitogen-Activated Protein Kinases
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| pubmed:year |
2009
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| pubmed:articleTitle |
Glycogen synthase kinase-3 negatively regulates anti-inflammatory interleukin-10 for lipopolysaccharide-induced iNOS/NO biosynthesis and RANTES production in microglial cells.
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| pubmed:affiliation |
Institute of Clinical Medicine, National Cheng Kung University Medical College, Tainan, Taiwan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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