title: Diarylheptanoid hirsutenone prevents tumor necrosis factor-alpha-stimulated production of inflammatory mediators in human keratinocytes through NF-kappaB inhibition.
abstract: Keratinocytes may play an important role in the pathogenesis of skin disease in atopic dermatitis. Diarylheptanoids such as oregonin and hirstanonol are demonstrated to have anti-inflammatory and anti-oxidant effects. The present study was to investigate the effect of hirsutenone, one of the diarylheptanoids, against tumor necrosis factor (TNF)-alpha-stimulated responses in human keratinocytes. Hirsutenone attenuated the TNF-alpha-induced production of cytokine IL-8, prostaglandin E(2) and chemokine CCL27, and the formation of reactive oxygen/nitrogen species in keratinocytes. Immunosuppressants (dexamethasone and cyclosporin A) inhibited the TNF-alpha-elicited formation of IL-8, prostaglandin E(2) and CCL27, but did not affect formation of reactive species. Bay 11-7085 (an inhibitor of NF-kappaB activation) and anti-oxidant N-acetylcysteine attenuated the TNF-alpha-induced formation of inflammatory mediators and reactive species. Hirsutenone, dexamethasone, cyclosporin A and Bay 11-7085 inhibited the TNF-alpha-induced phosphorylation of inhibitory kappaB and the activation of nuclear factor (NF)-kappaB. The results show that hirsutenone seems to reduce the TNF-alpha-stimulated production of inflammatory mediators in keratinocytes by suppressing the activation of NF-kappaB that may be mediated by reactive oxygen species. The findings suggest that hirsutenone may exert an inhibitory effect against the pro-inflammatory mediator-induced skin disease.
authors.affiliation: Department of Pharmacology, Chung-Ang University, Seoul, South Korea. leecs@cau.ac.kr
authors.forename: Chung Soo
authors.initials: CS
authors.lastname: Lee
authors.forename: Hyun Hee
authors.initials: HH
authors.lastname: Ko
authors.forename: Seong Jun
authors.initials: SJ
authors.lastname: Seo
authors.forename: Young Wook
authors.initials: YW
authors.lastname: Choi
authors.forename: Min Won
authors.initials: MW
authors.lastname: Lee
authors.forename: Soon Chul
authors.initials: SC
authors.lastname: Myung
authors.forename: Hyoweon
authors.initials: H
authors.lastname: Bang
mesh_terms: D029661:Alnus / Q000276:immunology*; D002396:Catechols / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D054425:Chemokine CCL27 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology; D036381:Diarylheptanoids / Q000737:chemistry / Q000494:pharmacology*; D015232:Dinoprostone / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D008517:Phytotherapy; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D002396:Catechols; D054425:Chemokine CCL27; D036381:Diarylheptanoids; D016209:Interleukin-8; D016328:NF-kappa B; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; C508777:hirsutenone; D015232:Dinoprostone