Abstract
Microbial products, including lipopolysaccharides, may be involved in the pathogenesis of inflammatory skin diseases. We examined the effect of hirsutenoxime on the Toll-like receptor 4-mediated activation of Akt and nuclear factor (NF)-κB in lipopolysaccharide-stimulated keratinocytes. Hirsutenoxime, a cell signaling Akt inhibitor, and Bay 11-7085, an inhibitor of NF-κB activation, attenuated the lipopolysaccharide-induced expression of Toll-like receptor 4, activation of NF-κB and Akt, and the production of chemokines and reactive oxygen/nitrogen species. Hirsutenoxime may reduce the Toll-like receptor 4 expression-mediated NF-κB activation, which is regulated by the Akt pathway in keratinocytes exposed to lipopolysaccharides. This effect may reduce the skin inflammatory response.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alnus / chemistry*
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Anti-Inflammatory Agents / pharmacology*
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Anti-Inflammatory Agents / therapeutic use
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Antioxidants / isolation & purification
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Antioxidants / pharmacology
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Antioxidants / therapeutic use
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Chemokines / metabolism
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Diarylheptanoids / isolation & purification
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Diarylheptanoids / pharmacology*
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Diarylheptanoids / therapeutic use
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Humans
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Inflammation / drug therapy
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Inflammation / metabolism
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Keratinocytes / drug effects*
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Keratinocytes / metabolism
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Lipopolysaccharides
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NF-kappa B / metabolism*
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Oximes / isolation & purification
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Oximes / pharmacology*
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Oximes / therapeutic use
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Plant Extracts / chemistry
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Plant Extracts / pharmacology
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Plant Extracts / therapeutic use
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Proto-Oncogene Proteins c-akt / metabolism*
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Reactive Nitrogen Species / metabolism
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Reactive Oxygen Species / metabolism
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Skin Diseases / drug therapy*
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Skin Diseases / metabolism
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Toll-Like Receptor 4 / metabolism*
Substances
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1,7-bis(3,4-dihydroxyphenyl)hept-4-en-3-one oxime
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Anti-Inflammatory Agents
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Antioxidants
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Chemokines
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Diarylheptanoids
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Lipopolysaccharides
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NF-kappa B
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Oximes
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Plant Extracts
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Reactive Nitrogen Species
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Reactive Oxygen Species
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TLR4 protein, human
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Toll-Like Receptor 4
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Proto-Oncogene Proteins c-akt