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Int J Mol Sci. 2019 May 7;20(9). pii: E2242. doi: 10.3390/ijms20092242.

Transcriptomic Analysis Reveals Priming of The Host Antiviral Interferon Signaling Pathway by Bronchobini® Resulting in Balanced Immune Response to Rhinovirus Infection in Mouse Lung Tissue Slices.

Author information

1
Department of Preclinical Pharmacology and In Vitro Toxicology, Fraunhofer Institute for Toxicology and Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Member of Fraunhofer international Consortium for Anti-Infective Research (iCAIR), 30625 Hannover, Germany. stella.reamon-buettner@item.fraunhofer.de.
2
Department of Preclinical Pharmacology and In Vitro Toxicology, Fraunhofer Institute for Toxicology and Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Member of Fraunhofer international Consortium for Anti-Infective Research (iCAIR), 30625 Hannover, Germany. monika.niehof@item.fraunhofer.de.
3
Heel GmbH, 76532 Baden-Baden, Germany. natalie.hirth@heel.de.
4
Department of Preclinical Pharmacology and In Vitro Toxicology, Fraunhofer Institute for Toxicology and Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Member of Fraunhofer international Consortium for Anti-Infective Research (iCAIR), 30625 Hannover, Germany. olga.danov@item.fraunhofer.de.
5
Department of Preclinical Pharmacology and In Vitro Toxicology, Fraunhofer Institute for Toxicology and Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Member of Fraunhofer international Consortium for Anti-Infective Research (iCAIR), 30625 Hannover, Germany. helena.obernolte@item.fraunhofer.de.
6
Department of Preclinical Pharmacology and In Vitro Toxicology, Fraunhofer Institute for Toxicology and Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Member of Fraunhofer international Consortium for Anti-Infective Research (iCAIR), 30625 Hannover, Germany. armin.braun@item.fraunhofer.de.
7
Heel GmbH, 76532 Baden-Baden, Germany. juergen.warnecke@heel.de.
8
Department of Preclinical Pharmacology and In Vitro Toxicology, Fraunhofer Institute for Toxicology and Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Member of Fraunhofer international Consortium for Anti-Infective Research (iCAIR), 30625 Hannover, Germany. katherina.sewald@item.fraunhofer.de.
9
Department of Preclinical Pharmacology and In Vitro Toxicology, Fraunhofer Institute for Toxicology and Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Member of Fraunhofer international Consortium for Anti-Infective Research (iCAIR), 30625 Hannover, Germany. sabine.wronski@item.fraunhofer.de.

Abstract

Rhinovirus (RV) is the predominant virus causing respiratory tract infections. Bronchobini® is a low dose multi component, multi target preparation used to treat inflammatory respiratory diseases such as the common cold, described to ease severity of symptoms such as cough and viscous mucus production. The aim of the study was to assess the efficacy of Bronchobini® in RV infection and to elucidate its mode of action. Therefore, Bronchobini®'s ingredients (BRO) were assessed in an ex vivo model of RV infection using mouse precision-cut lung slices, an organotypic tissue capable to reflect the host immune response to RV infection. Cytokine profiles were assessed using enzyme-linked immunosorbent assay (ELISA) and mesoscale discovery (MSD). Gene expression analysis was performed using Affymetrix microarrays and ingenuity pathway analysis. BRO treatment resulted in the significant suppression of RV-induced antiviral and pro-inflammatory cytokine release. Transcriptome analysis revealed a multifactorial mode of action of BRO, with a strong inhibition of the RV-induced pro-inflammatory and antiviral host response mediated by nuclear factor kappa B (NFkB) and interferon signaling pathways. Interestingly, this was due to priming of these pathways in the absence of virus. Overall, BRO exerted its beneficial anti-inflammatory effect by priming the antiviral host response resulting in a reduced inflammatory response to RV infection, thereby balancing an otherwise excessive inflammatory response.

KEYWORDS:

Bronchobini®; immunomodulation; interferon signaling pathway; precision-cut lung slices; rhinovirus; transcriptomics

PMID:
31067687
DOI:
10.3390/ijms20092242
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