Cafestol, a Coffee-Specific Diterpene, Is a Novel Extracellular Signal-Regulated Kinase Inhibitor with AP-1-Targeted Inhibition of Prostaglandin E2 Production in Lipopolysaccharide-Activated Macrophages
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概要
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Coffee is a popular beverage worldwide with various nutritional benefits. Diterpene cafestol, one of the major components of coffee, contributes to its beneficial effects through various biological activities such as chemopreventive, antitumorigenic, hepatoprotective, antioxidative and antiinflammatory effects. In this study, we examined the precise molecular mechanism of the antiinflammatory activity of cafestol in terms of prostaglandin E2 (PGE2) production, a critical factor involved in inflammatory responses. Cafestol inhibited both PGE2 production and the mRNA expression of cyclooxygenase (COX)-2 from lipopolysaccharide (LPS)-treated RAW264.7 cells. Interestingly, this compound strongly decreased the translocation of c-Jun into the nucleus and AP-1 mediated luciferase activity. In kinase assays using purified extracellular signal-regulated kinase 2 (ERK2) or immunoprecipitated ERK prepared from LPS-treated cells in the presence or absence of cafestol, it was found that this compound can act as an inhibitor of ERK2 but not of ERK1 and mitogen-activated protein kinase kinase 1 (MEK 1). Therefore our data suggest that cafestol may be a novel ERK inhibitor with AP-1-targeted inhibitory activity against PGE2 production in LPS-activated RAW264.7 cells.
著者
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Cho Jae
School Of Bioscience And Biotechnology And Inst. Of Bioscience And Biotechnology Kangwon National Un
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Lee Jaehwi
College of Pharmacy, Chung-Ang University
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Shen Ting
School of Bioscience and Biotechnology, Kangwon National University
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Kim Seong
Laboratory of Chemical Genomics, Korea Research Institute of Chemical Technology
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Kim Tae
Department of Advanced Materials Engineering, Sungkyunkwan University, Suwon, Gyeonggi 440-746, Republic Korea
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Lee Eunji
College of Pharmacy, Chung-Ang University
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Shen Ting
School of Bioscience and Biotechnology, and Institute of Bioscience and Biotechnology, Kangwon National University
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