title: SIRT1, a Class III Histone Deacetylase, Regulates LPS-Induced Inflammation in Human Keratinocytes and Mediates the Anti-Inflammatory Effects of Hinokitiol.
abstract: Skin inflammation is a response of the immune system to infection and injury. In this study, we report that hinokitiol, a tropolone-related natural compound that exhibits antioxidant, anti-inflammatory, and anticancer properties in various cell types, can modulate the inflammatory responses of primary human keratinocytes challenged with lipopolysaccharide (LPS). Hinokitiol treatment inhibited LPS-mediated up-regulation of proinflammatory factors including tumor necrosis factor alpha, IL-6, and prostaglandin E2(PGE2). NF-κB activation and cell migration induced by LPS were blocked in keratinocytes treated with hinokitiol. Sirt1, a class Ⅲ histone deacetylase, was up-regulated by hinokitiol treatment, and the inhibition of Sirt1 activity using a pharmacological inhibitor or genetic silencing blocked hinokitiol-mediated anti-inflammatory effects. Further, hyperactivation of Sirt1 deacetylase using an adenoviral vector also attenuated LPS-induced inflammatory responses. We thus show that hinokitiol can attenuate LPS-mediated proinflammatory signals via Sirt1 histone deacetylase activation in primary human keratinocytes and suggest that hinokitiol may be a potential therapeutic agent in skin inflammatory diseases like psoriasis.
authors.affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk, South Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk, South Korea.
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Moon
authors.affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk, South Korea.
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk, South Korea. Electronic address: sypark@chonbuk.ac.kr.
authors.forename: Sang-Youel
authors.initials: SY
authors.lastname: Park
mesh_terms: D000704:Analysis of Variance; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D004347:Drug Interactions; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D039821:Monoterpenes / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D056564:Sirtuin 1 / Q000187:drug effects / Q000378:metabolism*; D014334:Tropolone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D039821:Monoterpenes; D014334:Tropolone; C447939:SIRT1 protein, human; D056564:Sirtuin 1; C009479:beta-thujaplicin