1,8-Cineole potentiates IRF3-mediated antiviral response in human stem cells and in an ex vivo model of rhinosinusitis

© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2016

Erschienen:

2016

Enthalten in:

Zur Gesamtaufnahme - volume:130

Enthalten in:

Clinical science (London, England : 1979) - 130(2016), 15 vom: 01. Aug., Seite 1339-52

Sprache:

Englisch

Beteiligte Personen:

Müller, Janine [VerfasserIn]
Greiner, Johannes F W [VerfasserIn]
Zeuner, Marie [VerfasserIn]
Brotzmann, Viktoria [VerfasserIn]
Schäfermann, Johanna [VerfasserIn]
Wieters, Frederique [VerfasserIn]
Widera, Darius [VerfasserIn]
Sudhoff, Holger [VerfasserIn]
Kaltschmidt, Barbara [VerfasserIn]
Kaltschmidt, Christian [VerfasserIn]

Links:

Volltext

Themen:

1
8-cineole
Anti-Inflammatory Agents
Antiviral Agents
Common cold
Cyclohexanols
Eucalyptol
Human ex vivo model
IRF3
IRF3 protein, human
Interferon Regulatory Factor-3
Journal Article
Lipopolysaccharides
Monoterpenes
NF-κB
O84C90HH2L
Poly(I:C)
Poly I-C
Polynucleotides
RELA protein, human
RV6J6604TK
Transcription Factor RelA

Anmerkungen:

Date Completed 03.07.2017

Date Revised 03.12.2018

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1042/CS20160218

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM259874124