1. Genome-Wide Gene Expression Analysis Reveals Unique Genes Signatures of Epithelial Reorganization in Primary Airway Epithelium Induced by Type-I, -II and -III Interferons
- Author
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Anna Erb, Ulrich M. Zissler, Madlen Oelsner, Adam M. Chaker, Carsten B. Schmidt-Weber, and Constanze A. Jakwerth
- Subjects
Clinical Biochemistry ,Biomedical Engineering ,Gene Expression ,General Medicine ,Antiviral Agents ,Epithelium ,Analytical Chemistry ,ddc ,Article ,microarray ,gene expression analysis ,airway epithelial ,type-I ,II and -III Interferons ,epithelial integrity ,remodeling ,Interferon Type I ,ii And -iii Interferons ,Airway Epithelial ,Epithelial Integrity ,Gene Expression Analysis ,Microarray ,Remodeling ,Type-i ,Instrumentation ,Engineering (miscellaneous) ,Biotechnology - Abstract
Biosensors such as toll-like receptors (TLR) induce the expression of interferons (IFNs) after viral infection that are critical to the first step in cell-intrinsic host defense mechanisms. Their differential influence on epithelial integrity genes, however, remains elusive. A genome-wide gene expression biosensor chip for gene expression sensing was used to examine the effects of type-I, -II, and -III IFN stimulation on the epithelial expression profiles of primary organotypic 3D air-liquid interface airway cultures. All types of IFNs induced similar interferon-stimulated genes (ISGs): OAS1, OAS2, and IFIT2. However, they differentially induced transcription factors, epithelial modulators, and pro-inflammatory genes. Type-I IFN-induced genes were associated with cell–cell adhesion and tight junctions, while type-III IFNs promoted genes important for transepithelial transport. In contrast, type-II IFN stimulated proliferation-triggering genes associated and enhanced pro-inflammatory mediator secretion. In conclusion, with our microarray system, we provide evidence that the three IFN types exceed their antiviral ISG-response by inducing distinct remodeling processes, thereby likely strengthening the epithelial airway barrier by enhancing cross-cell-integrity (I), transepithelial transport (III) and finally reconstruction through proliferation (II).
- Published
- 2021