title: Histone deacetylase inhibitors up-regulate LL-37 expression independent of toll-like receptor mediated signalling in airway epithelial cells.
abstract: HDAC inhibitors have been proposed as anticancer agents. However, their roles in innate genes expression remain not well known. Cathelicidin LL-37 is one of the few human bactericidal peptides, but the regulation of histone acetylation on LL-37 expression in airway epithelium remains largely unknown. Therefore, we investigated the effects of two non-selective HDACi, trichostatin A (TSA) and sodium butyrate (SB), on the expression of the cathelicidin LL-37 in human airway epithelial cells. LL37 in human NCI-H292 airway epithelial cells and the primary cultures of normal nasal epithelial cells(PNEC) in response to HDAC inhibitors with or without poly (I:C) stimulation was assessed using real-time PCR and western blot. In parallel, IL-6 expression was evaluated by ELISA. Our results showed that HDAC inhibitors up-regulated LL-37 gene expression independent of poly (I:C) stimulation in PNEC as well as in NCI-H292 cells. HDAC inhibitors increased LL37 protein expression in NCI-H292 cells but not in PNEC. In addition, HDAC inhibitors significantly inhibited poly (I:C)-induced IL-6 production in both of the epithelial cells. In conclusion, HDAC inhibitors directly up-regulated LL-37 gene expression in human airway epithelial cells.
authors.affiliation: Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, 200031, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, 200031, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, the Netherlands.|Hannover Medical School, SFB 587, Immune reactions of the lung in infection and allergy, Hannover, Germany.|Department of Airway Immunology, Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany.
authors.forename: Kristina Irene Lisolette
authors.initials: KIL
authors.lastname: Roschmann
authors.affiliation: Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Danielle
authors.initials: D
authors.lastname: van Egmond
authors.affiliation: Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Korneliusz
authors.initials: K
authors.lastname: Golebski
authors.affiliation: Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Wytske Johanna
authors.initials: WJ
authors.lastname: Fokkens
authors.affiliation: Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, 200031, China.
authors.forename: Dehui
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Cornelis Maria
authors.initials: CM
authors.lastname: van Drunen