Müller Janine, Greiner Johannes F W, Zeuner Marie, Brotzmann Viktoria, Schäfermann Johanna, Wieters Frederique, Widera Darius, Sudhoff Holger, Kaltschmidt Barbara, Kaltschmidt Christian
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.
Department of Otolaryngology, Head and Neck Surgery, Klinikum Bielefeld, D-33604 Bielefeld, Germany Department of Cell Biology, University of Bielefeld, 33619 Bielefeld, Germany.
Clin Sci (Lond). 2016 Aug 1;130(15):1339-52. doi: 10.1042/CS20160218. Epub 2016 Apr 25.
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.
普通感冒是由病毒引起的最常见的人类炎症性疾病之一，并且会引发细菌的重复感染，进而导致鼻窦炎或肺炎。药物Soledum的活性成分1,8-桉叶素常用于治疗呼吸道炎症性疾病。然而，1,8-桉叶素治疗呼吸道原发性病毒感染的潜力仍不明确。在本研究中，我们首次证明1,8-桉叶素增强了聚肌胞苷酸（poly(I:C)）诱导的抗病毒转录因子干扰素调节因子3（IRF3）的活性，同时降低了人细胞系、下鼻甲干细胞（ITSCs）和体外培养的人鼻黏膜中的促炎核因子（NF）-κB活性。与单独使用poly(I:C)相比，细胞系用poly(I:C)和1,8-桉叶素共同处理后，IRF3报告基因活性显著增加，而NF-κB活性降低。因此，与poly(I:C)处理方法相比，1,8-桉叶素和poly(I:C)处理导致ITSCs和鼻窦炎人离体模型中IRF3的核转位增加。与模拟细菌感染的LPS处理细胞相比，用脂多糖（LPS）和1,8-桉叶素处理的ITSCs和切片培养物中IRF3的核转位显著增加。我们的研究结果强烈表明，1,8-桉叶素除了对促炎NF-κB信号传导具有抑制作用外，还增强了IRF3的抗病毒活性，因此可能会拓宽其应用领域。
