Abstract
Nuclear factor-kappaB (NF-kappaB) is a critical transcription factor for maximal expression of many of the cytokines that are involved in the pathogenesis of inflammatory diseases. In this study, we found that pinosylvin, a natural stilbenoid that is a component of the pine leaf (Pinus densiflora), significantly inhibited LPS-induced NF-kappaB activation in a concentration-dependent manner. Additionally, pinosylvin was found to inhibit the LPS-induced phosphorylation and degradation of IkappaB alpha in THP-1 cells. Therefore, we have attempted to determine whether pinosylvin can inhibit the expression of cytokines possessing NF-kappaB binding sites in their promoter regions. In a consistent result, pinosylvin inhibited LPS-induced production of TNF alpha and interleukin-8 (IL-8). Taken together, these results show that pinosylvin suppresses the production of pro-inflammatory mediators through the inhibition of the NF-kappaB signaling pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Inflammatory Agents / pharmacology*
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Binding Sites
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Cell Line
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Cyclooxygenase 2 / genetics
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Cyclooxygenase 2 Inhibitors / pharmacology
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Cytokines / metabolism*
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Gene Expression Regulation / drug effects
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Genes, Reporter
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Humans
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I-kappa B Proteins / metabolism
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Interleukin-8 / antagonists & inhibitors
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Interleukin-8 / genetics
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Lipopolysaccharides / antagonists & inhibitors
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Luciferases / analysis
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism
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NF-kappa B / physiology*
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Phosphorylation
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Pinus / chemistry
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Promoter Regions, Genetic
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Signal Transduction / drug effects
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Stilbenes / chemistry
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Stilbenes / pharmacology*
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / genetics
Substances
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Anti-Inflammatory Agents
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Cyclooxygenase 2 Inhibitors
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Cytokines
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I-kappa B Proteins
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Interleukin-8
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Lipopolysaccharides
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NF-kappa B
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Stilbenes
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Tumor Necrosis Factor-alpha
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pinosylvin
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Luciferases
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Cyclooxygenase 2