title: 1,8-Cineole potentiates IRF3-mediated antiviral response in human stem cells and in an ex vivo model of rhinosinusitis.
abstract: The common cold is one of the most frequent human inflammatory diseases caused by viruses and can facilitate bacterial superinfections, resulting in sinusitis or pneumonia. The active ingredient of the drug Soledum, 1,8-cineole, is commonly applied for treating inflammatory diseases of the respiratory tract. However, the potential for 1,8-cineole to treat primary viral infections of the respiratory tract remains unclear. In the present study, we demonstrate for the first time that 1,8-cineole potentiates poly(I:C)-induced activity of the antiviral transcription factor interferon regulatory factor 3 (IRF3), while simultaneously reducing proinflammatory nuclear factor (NF)-κB activity in human cell lines, inferior turbinate stem cells (ITSCs) and in ex vivo cultivated human nasal mucosa. Co-treatment of cell lines with poly(I:C) and 1,8-cineole resulted in significantly increased IRF3 reporter gene activity compared with poly(I:C) alone, whereas NF-κB activity was reduced. Accordingly, 1,8-cineole- and poly(I:C) treatment led to increased nuclear translocation of IRF3 in ITSCs and a human ex vivo model of rhinosinusitis compared with the poly(I:C) treatment approach. Nuclear translocation of IRF3 was significantly increased in ITSCs and slice cultures treated with lipopolysaccharide (LPS) and 1,8-cineole compared with the LPS-treated cells mimicking bacterial infection. Our findings strongly suggest that 1,8-cineole potentiates the antiviral activity of IRF3 in addition to its inhibitory effect on proinflammatory NF-κB signalling, and may thus broaden its field of application.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Klinikum Bielefeld, D-33604 Bielefeld, Germany Department of Cell Biology, University of Bielefeld, 33619 Bielefeld, Germany AG Molecular Neurobiology, University of Bielefeld, 33619 Bielefeld, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Müller
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Klinikum Bielefeld, D-33604 Bielefeld, Germany Department of Cell Biology, University of Bielefeld, 33619 Bielefeld, Germany.
authors.forename: Johannes F W
authors.initials: JF
authors.lastname: Greiner
authors.affiliation: Department of Cell Biology, University of Bielefeld, 33619 Bielefeld, Germany Reading School of Pharmacy, University of Reading, PO Box 226, Whiteknights, Reading, Berkshire RG6 6AP, UK.
authors.forename: Marie
authors.initials: M
authors.lastname: Zeuner
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Klinikum Bielefeld, D-33604 Bielefeld, Germany Department of Cell Biology, University of Bielefeld, 33619 Bielefeld, Germany.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Brotzmann
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Klinikum Bielefeld, D-33604 Bielefeld, Germany Department of Cell Biology, University of Bielefeld, 33619 Bielefeld, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Schäfermann
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Klinikum Bielefeld, D-33604 Bielefeld, Germany Department of Cell Biology, University of Bielefeld, 33619 Bielefeld, Germany.
authors.forename: Frederique
authors.initials: F
authors.lastname: Wieters
authors.affiliation: Department of Cell Biology, University of Bielefeld, 33619 Bielefeld, Germany Reading School of Pharmacy, University of Reading, PO Box 226, Whiteknights, Reading, Berkshire RG6 6AP, UK.
authors.forename: Darius
authors.initials: D
authors.lastname: Widera
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Klinikum Bielefeld, D-33604 Bielefeld, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Sudhoff
authors.affiliation: Department of Cell Biology, University of Bielefeld, 33619 Bielefeld, Germany AG Molecular Neurobiology, University of Bielefeld, 33619 Bielefeld, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kaltschmidt
authors.affiliation: Department of Cell Biology, University of Bielefeld, 33619 Bielefeld, Germany c.kaltschmidt@uni-bielefeld.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Kaltschmidt
mesh_terms: D021581:Active Transport, Cell Nucleus; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D003511:Cyclohexanols / Q000494:pharmacology*; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D004305:Dose-Response Relationship, Drug; D000077591:Eucalyptol; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D039821:Monoterpenes / Q000494:pharmacology*; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D011070:Poly I-C; D011119:Polynucleotides / Q000494:pharmacology; D034622:RNA Interference; D012220:Rhinitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D012852:Sinusitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D013234:Stem Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D013997:Time Factors; D046509:Tissue Culture Techniques; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014420:Turbinates / Q000187:drug effects / Q000378:metabolism / Q000821:virology
chemical_list: D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents; D003511:Cyclohexanols; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D008070:Lipopolysaccharides; D039821:Monoterpenes; D011119:Polynucleotides; C498143:RELA protein, human; D051996:Transcription Factor RelA; D011070:Poly I-C; D000077591:Eucalyptol
keywords: 1; 8-cineole; IRF3; NF-κB; common cold; human ex vivo model; poly(I:C)