Source:http://linkedlifedata.com/resource/pubmed/id/17240450
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
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| pubmed:dateCreated |
2007-2-19
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| pubmed:abstractText |
The mis-regulation of nuclear factor-kappa B (NF-kappaB) signal pathway is involved in a variety of inflammatory diseases that leds to the production of inflammatory mediators. Our studies using human U937 promonocytes cells suggested that magnolol, a low molecular weight lignan isolated from the medicinal plant Magnolia officinalis, differentially down-regulated the pharmacologically induced expression of NF-kappaB-regulated inflammatory gene products MMP-9, IL-8, MCP-1, MIP-1alpha, TNF-alpha. Pre-treatment of magnolol blocked TNF-alpha-induced NF-kappaB activation in different cell types as evidenced by EMSA. Magnolol did not directly affect the binding of p65/p50 heterodimer to DNA. Immunoblot analysis demonstrated that magnolol inhibited the TNF-alpha-stimulated phosphorylation and degradation of the cytosolic NF-kappaB inhibitor IkappaBalpha and the effects were dose-dependent. Mechanistically, a non-radioactive IkappaB kinases (IKK) assay using immunoprecipitated IKKs protein demonstrated that magnolol inhibited both intrinsic and TNF-alpha-stimulated IKK activity, thus suggesting a critical role of magnolol in abrogating the phosphorylation and degradation of IkappaBalpha. The involvement of IKK was further verified in a HeLa cell NF-kappaB-dependent luciferase reporter system. In this system magnolol suppressed luciferase expression stimulated by TNF-alpha and by the transient transfection and expression of NIK (NF-kappaB-inducing kinase), wild type IKKbeta, constitutively active IKKalpha and IKKbeta, or the p65 subunit. Magnolol was also found to inhibit the nuclear translocation and phosphorylation of p65 subunit of NF-kappaB. In line with the observation that NF-kappaB activation may up-regulate anti-apoptotic genes, it was shown in U937 cells that magnolol enhanced TNF-alpha-induced apoptotic cell death. Our results suggest that magnolol or its derivatives may have potential anti-inflammatory actions through IKK inactivation.
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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/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/Biphenyl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Lignans,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 9,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B p50 Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor RelA,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/magnolol
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| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
0161-5890
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
44
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2647-58
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:17240450-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:17240450-Apoptosis,
pubmed-meshheading:17240450-Biphenyl Compounds,
pubmed-meshheading:17240450-Cell Line, Tumor,
pubmed-meshheading:17240450-Cytokines,
pubmed-meshheading:17240450-Dimerization,
pubmed-meshheading:17240450-Down-Regulation,
pubmed-meshheading:17240450-Gene Expression Regulation,
pubmed-meshheading:17240450-Humans,
pubmed-meshheading:17240450-I-kappa B Kinase,
pubmed-meshheading:17240450-Lignans,
pubmed-meshheading:17240450-Lipopolysaccharides,
pubmed-meshheading:17240450-Matrix Metalloproteinase 9,
pubmed-meshheading:17240450-NF-kappa B,
pubmed-meshheading:17240450-NF-kappa B p50 Subunit,
pubmed-meshheading:17240450-Phosphorylation,
pubmed-meshheading:17240450-Transcription Factor RelA,
pubmed-meshheading:17240450-Tumor Necrosis Factor-alpha
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| pubmed:year |
2007
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| pubmed:articleTitle |
Magnolol suppresses NF-kappaB activation and NF-kappaB regulated gene expression through inhibition of IkappaB kinase activation.
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| pubmed:affiliation |
Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon Tong, Hong Kong SAR, China.
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| pubmed:publicationType |
Journal Article
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