title: Rotundarpene inhibits toll-like receptor 2 activation-induced production of inflammatory mediators in keratinocytes by suppressing the Akt and NF-κB pathways.
abstract: Microbial components have been shown to be involved in the pathogenesis of inflammatory skin diseases. The extract of from the barks of Ilex rotunda Thunb has demonstrated anti-inflammatory and anti-oxidant effects. However, the effect of hemiterpene rotundarpene (4-caffeoyl-3-methyl-but-2-ene-1,4-diol) on the Toll-like receptor (TLR)-2 activation-induced production of inflammatory mediators in keratinocytes has not been studied. Using human keratinocytes, we investigated the effect of rotundarpene on the inflammatory mediator production in relation to the TLR-2-mediated-Akt and NF-κB pathways, which regulates the transcription genes involved in immune and inflammatory responses. Rotundarpene, Akt inhibitor, Bay 11-7085 and N-acetylcysteine each attenuated the lipoteichoic acid- or peptidoglycan-induced production of cytokines and chemokines, expression of TLR-2, activation of NF-κB and Akt, and formation of reactive oxygen species in keratinocytes. Cyclosporine A attenuated the bacterial component-induced production of inflammatory mediators but did not reduce the formation of reactive oxygen species. The results show that rotundarpene may attenuate the bacterial component-stimulated production of inflammatory mediators in keratinocytes by suppressing the TLR-2-mediated activation of the Akt and NF-κB pathways. The effect of rotundarpene may be attributed to its inhibitory effect on the formation of reactive oxygen species. Rotundarpene may exert a preventive effect against the bacterial component-mediated inflammatory skin diseases.
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, South Korea.
authors.forename: Yun Jeong
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, South Korea.
authors.forename: Eun Byul
authors.initials: EB
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, SoonChunHyang University Hospital, Bucheon City, Kyung-Gi-Do 420-767, South Korea.
authors.forename: Min Sung
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Deparment of Dermatology, Chung-Ang University Hospital, Seoul 156-755, South Korea.
authors.forename: Seong Jun
authors.initials: SJ
authors.lastname: Seo
authors.affiliation: Pharmacognosy Laboratory, College of Pharmacy, Chung-Ang University, Seoul 156-756, South Korea.
authors.forename: Manh Heun
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Pharmacognosy Laboratory, College of Pharmacy, Chung-Ang University, Seoul 156-756, South Korea.
authors.forename: Min Won
authors.initials: MW
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, South Korea. Electronic address: leecs@cau.ac.kr.
authors.forename: Chung Soo
authors.initials: CS
authors.lastname: Lee
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002109:Caffeic Acids / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D045782:Hemiterpenes / Q000494:pharmacology*; D006801:Humans; D030017:Ilex; D015603:Keratinocytes; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D024301:Plant Bark; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013682:Teichoic Acids / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D002109:Caffeic Acids; D016207:Cytokines; D045782:Hemiterpenes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C495342:TLR2 protein, human; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; C000591680:rotundarpene; C009900:lipoteichoic acid; D051057:Proto-Oncogene Proteins c-akt; D015232:Dinoprostone
keywords: Akt and NF-κB pathways; Inflammatory mediator production; Keratinocytes; Microbial components; Rotundarpene; Toll-like receptor-2