title: 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.
abstract: 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 E(2) (PGE(2)) production, a critical factor involved in inflammatory responses. Cafestol inhibited both PGE(2) 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 PGE(2) production in LPS-activated RAW264.7 cells.
authors.affiliation: School of Bioscience and Biotechnology, Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Ting
authors.initials: T
authors.lastname: Shen
authors.forename: Jaehwi
authors.initials: J
authors.lastname: Lee
authors.forename: Eunji
authors.initials: E
authors.lastname: Lee
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Kim
authors.forename: Tae Woong
authors.initials: TW
authors.lastname: Kim
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D003069:Coffee / Q000737:chemistry*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D004224:Diterpenes / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides; D008156:Luciferases / Q000378:metabolism; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D003069:Coffee; D004224:Diterpenes; D008070:Lipopolysaccharides; D010936:Plant Extracts; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; C053400:cafestol; D008156:Luciferases; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D015232:Dinoprostone