Protein Coding and Long Noncoding RNA (lncRNA) Transcriptional Landscape in SARS-CoV-2 Infected Bronchial Epithelial Cells Highlight a Role for Interferon and Inflammatory Response

The global spread of COVID-19, caused by pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for an imminent response from medical research communities to better understand this rapidly spreading infection. Employing multiple bioinformatics and computational pipelines on transcriptome data from primary normal human bronchial epithelial cells (NHBE) during SARS-CoV-2 infection revealed activation of several mechanistic networks, including those involved in immunoglobulin G (IgG) and interferon lambda (IFNL) in host cells. Induction of acute inflammatory response and activation of tumor necrosis factor (TNF) was prominent in SARS-CoV-2 infected NHBE cells. Additionally, disease and functional analysis employing ingenuity pathway analysis (IPA) revealed activation of functional categories related to cell death, while those associated with viral infection and replication were suppressed. Several interferon (IFN) responsive gene targets (IRF9, IFIT1, IFIT2, IFIT3, IFITM1, MX1, OAS2, OAS3, IFI44 and IFI44L) were highly upregulated in SARS-CoV-2 infected NBHE cell, implying activation of antiviral IFN innate response. Gene ontology and functional annotation of differently expressed genes in patient lung tissues with COVID-19 revealed activation of antiviral response as the hallmark. Mechanistic network analysis in IPA identified 14 common activated, and 9 common suppressed networks in patient tissue, as well as in the NHBE cell model, suggesting a plausible role for these upstream regulator networks in the pathogenesis of COVID-19. Our data revealed expression of several viral proteins in vitro and in patient-derived tissue, while several host-derived long noncoding RNAs (lncRNAs) were identified. Our data highlights activation of IFN response as the main hallmark associated with SARS-CoV-2 infection in vitro and in human, and identified several differentially expressed lncRNAs during the course of infection, which could serve as disease biomarkers, while their precise role in the host response to SARS-CoV-2 remains to be investigated.

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Ambient fine particulate matter (PM2.5) induces oxidative stress and pro-inflammatory response via up-regulating the expression of CYP1A1/1B1 in human bronchial epithelial cells in vitro

Mutation Research/Genetic Toxicology and Environmental Mutagenesis ◽

10.1016/j.mrgentox.2018.12.005 ◽

2019 ◽

Vol 839 ◽

pp. 40-48 ◽

Cited By ~ 10

Author(s):

Qi Yuan ◽

Yaoyao Chen ◽

Xiaobo Li ◽

Zhengdong Zhang ◽

Haiyan Chu

Keyword(s):

Oxidative Stress ◽

Particulate Matter ◽

Epithelial Cells ◽

Inflammatory Response ◽

Fine Particulate Matter ◽

Bronchial Epithelial Cells ◽

Human Bronchial Epithelial Cells ◽

Bronchial Epithelial ◽

Fine Particulate

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COPD Is Associated with Elevated IFN-β Production by Bronchial Epithelial Cells Infected with RSV or hMPV

Viruses ◽

10.3390/v13050911 ◽

2021 ◽

Vol 13 (5) ◽

pp. 911

Author(s):

Natasha Collinson ◽

Natale Snape ◽

Kenneth Beagley ◽

Emmanuelle Fantino ◽

Kirsten Spann

Keyword(s):

Epithelial Cells ◽

Viral Infections ◽

Cell Model ◽

Bronchial Epithelial Cells ◽

Intrinsic Defect ◽

Bronchial Epithelial ◽

Copd Exacerbations ◽

Susceptibility To Infection ◽

Viral Shedding

IFN treatment may be a viable option for treating COPD exacerbations based on evidence of IFN deficiency in COPD. However, in vitro studies have used primarily influenza and rhinoviruses to investigate IFN responses. This study aims to investigate the susceptibility to infection and IFN response of primary bronchial epithelial cells (BECs) from COPD donors to infection with RSV and hMPV. BECs from five COPD and five healthy donors were used to establish both submerged monolayer and well-differentiated (WD) cultures. Two isolates of both RSV and hMPV were used to infect cells. COPD was not associated with elevated susceptibility to infection and there was no evidence of an intrinsic defect in IFN production in either cell model to either virus. Conversely, COPD was associated with significantly elevated IFN-β production in response to both viruses in both cell models. Only in WD-BECs infected with RSV was elevated IFN-β associated with reduced viral shedding. The role of elevated epithelial cell IFN-β production in the pathogenesis of COPD is not clear and warrants further investigation. Viruses vary in the responses that they induce in BECs, and so conclusions regarding antiviral responses associated with disease cannot be made based on single viral infections.

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PDE4 inhibitors have no effect on eotaxin expression in human primary bronchial epithelial cells.

Acta Biochimica Polonica ◽

10.18388/abp.2012_2124 ◽

2012 ◽

Vol 59 (3) ◽

Cited By ~ 1

Author(s):

Magdalena Paplińska-Goryca ◽

Ryszarda Chazan ◽

Hanna Grubek-Jaworska

Keyword(s):

Epithelial Cells ◽

Cell Model ◽

Mrna Level ◽

Allergic Inflammation ◽

Bronchial Epithelial Cells ◽

Experimental Conditions ◽

Bronchial Epithelial ◽

Mediators Of Inflammation ◽

Primary Bronchial Epithelial Cells

The bronchial epithelium is a very important factor during the inflammatory response, it produces many key regulators involved in the pathophysiology of asthma and COPD. Local influx of eosinophils, basophils, Th2 lymphocytes and macrophages is the source of many cytotoxic proteins, cytokines and other mediators of inflammation. These cells are attracted by eotaxins (eotaxin-1/CCL11, eotaxin-2/CCL24, eotaxin-3/CCL26). Inhibitors of phosphodiesterase 4 (PDE4) are new anti-inflammatory drugs which cause cAMP accumulation in the cell and inhibit numerous stages of allergic inflammation. The aim of our study was to evaluate the influence of PDE4 inhibitors: rolipram and RO-20-1724 on the expression of eotaxins in human primary bronchial epithelial cells. Cells were preincubated with PDE4 inhibitors for 1 hour and then stimulated with IL-4 or IL-13 alone or in combination with TNF-α. After 48 hours, eotaxin protein level was measured by ELISA and mRNA level by real time PCR. These cells produce CCL24 and CCL26. PDE4 inhibitors increased CCL24 and CCL26 mRNA level irrespectively of the used stimulators. Rolipram and RO-20-1724 had no effect on eotaxin protein production in our experimental conditions. Thus PDE4 inhibitors have no effect on eotaxin protein expression in human primary bronchial epithelial cells. In vitro experiments should be performed using a primary cell model rather than immortalized lines.

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