scholarly journals Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells

2014 ◽  
Vol 45 (2) ◽  
pp. 428-439 ◽  
Author(s):  
Aline Schögler ◽  
Brigitte S. Kopf ◽  
Michael R. Edwards ◽  
Sebastian L. Johnston ◽  
Carmen Casaulta ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pattern Recognition ◽  
Cell Death ◽  
Epithelial Cells ◽  
Bronchial Epithelial Cells ◽  
Pattern Recognition Receptor ◽  
Bronchial Epithelial ◽  
Pulmonary Exacerbations ◽  
Pre Treatment ◽  
Recognition Receptor

Virus-associated pulmonary exacerbations, often associated with rhinoviruses (RVs), contribute to cystic fibrosis (CF) morbidity. Currently, there are only a few therapeutic options to treat virus-induced CF pulmonary exacerbations. The macrolide antibiotic azithromycin has antiviral properties in human bronchial epithelial cells. We investigated the potential of azithromycin to induce antiviral mechanisms in CF bronchial epithelial cells.Primary bronchial epithelial cells from CF and control children were infected with RV after azithromycin pre-treatment. Viral RNA, interferon (IFN), IFN-stimulated gene and pattern recognition receptor expression were measured by real-time quantitative PCR. Live virus shedding was assessed by assaying the 50% tissue culture infective dose. Pro-inflammatory cytokine and IFN-β production were evaluated by ELISA. Cell death was investigated by flow cytometry.RV replication was increased in CF compared with control cells. Azithromycin reduced RV replication seven-fold in CF cells without inducing cell death. Furthermore, azithromycin increased RV-induced pattern recognition receptor, IFN and IFN-stimulated gene mRNA levels. While stimulating antiviral responses, azithromycin did not prevent virus-induced pro-inflammatory responses.Azithromycin pre-treatment reduces RV replication in CF bronchial epithelial cells, possibly through the amplification of the antiviral response mediated by the IFN pathway. Clinical studies are needed to elucidate the potential of azithromycin in the management and prevention of RV-induced CF pulmonary exacerbations.

scholarly journals 1187. CFTR Function Impacts Proinflammatory Cytokine Expression of Bronchial Epithelial Cells During Pseudomonas aeruginosa and Staphylococcus aureus Infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S617-S617
Author(s):  
Melissa S Phuong ◽  
Subash Sad
Keyword(s):  
Cystic Fibrosis ◽  
Immune Response ◽  
Cell Death ◽  
Epithelial Cells ◽  
Host Cell ◽  
Cytokine Expression ◽  
Bronchial Epithelial Cells ◽  
Macrophage Phenotype ◽  
Bronchial Epithelial ◽  
Host Cell Death

Abstract Background Cystic fibrosis (CF) is a genetic disease in which opportunistic respiratory infections are common, particularly with P. aeruginosa and S. aureus. It has been suggested that dysfunction in the cystic fibrosis transmembrane conductance regulator (CFTR) could impact host immune response to these infections. The aim of this study was to determine if dysfunction in the CFTR gene could impact host cell death and the expression of proinflammatory cytokines. Methods We used two human bronchial epithelial (HBE) cell lines NuLi-1 and CuFi-1, which were recovered from individuals without and with CF, respectively. THP-1 cells were also differentiated into a macrophage phenotype with 50ng/mL PMA, and 10 µM CFTRinh-172 was used to impair CFTR function in these cells. Laboratory reference strains PAO1 and S. aureus 6538 were used to conduct in vitro infections. Host cell death at various MOIs was evaluated using a neutral red uptake assay, and cytokine expression was measured using ELISAs. Results No differences in THP-1 cell death or cytokine expression were observed for infections with S. aureus 6538 or PAO1 with and without CFTRinh-172. No differences in cell death for infections with the HBE cells and either bacteria were noted. S. aureus 6538 induced higher levels of IL-1β when infecting CuFi-1 cells in comparison to NuLi-1 cells across all MOIs (P < 0.001) and induced higher levels of IL-6 at an MOI of 100 (P < 0.01). S. aureus 6538 also induced higher levels of IL-8 when infecting CuFi-1 cells in comparison to NuLi-1 at MOIs of 1 and 10 (P < 0.05 and P < 0.01, respectively). Meanwhile, PAO1 induced less IL-6 expression when infecting CuFI-1 cells at an MOI of 1 and 10 (P < 0.01 and P < 0.01, respectively). CuFi-1 cells infected with PAO1 had less IL-8 expression in comparison to infected NuLi-1 cells for all MOIs (P < 0.01), but no differences in IL-1β expression were observed when infecting either cell line with PAO1. Conclusion Bronchial epithelial cells with and without functional CFTR appear to respond differently to infections with either P. aeruginosa or S. aureus. Further elucidating how various immune response pathways are impacted by CFTR dysfunction may lead to alternative approaches to therapy to reduce morbidity observed among CF patients. Disclosures All Authors: No reported disclosures

Interaction of environmental Burkholderia cenocepacia strains with cystic fibrosis and non-cystic fibrosis bronchial epithelial cells in vitro

Microbiology ◽  
2012 ◽  
Vol 158 (5) ◽  
pp. 1325-1333 ◽  
Author(s):  
Annamaria Bevivino ◽  
Luisa Pirone ◽  
Ruth Pilkington ◽  
Noemi Cifani ◽  
Claudia Dalmastri ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Bronchial Epithelial Cells ◽  
Burkholderia Cenocepacia ◽  
Bronchial Epithelial

scholarly journals Additive effects of simulated microgravity and ionizing radiation in cell death, induction of ROS and expression of RAC2 in human bronchial epithelial cells

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Shaobo Tan ◽  
Weiwei Pei ◽  
Hao Huang ◽  
Guangming Zhou ◽  
Wentao Hu
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Ionizing Radiation ◽  
Simulated Microgravity ◽  
Biological Effects ◽  
Bronchial Epithelial Cells ◽  
Space Environment ◽  
Mechanistic Study ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial

Abstract Radiation and microgravity are undoubtedly two major factors in space environment that pose a health threat to astronauts. However, the mechanistic study of their interactive biological effects is lacking. In this study, human lung bronchial epithelial Beas-2B cells were used to study the regulation of radiobiological effects by simulated microgravity (using a three-dimensional clinostat). It was found that simulated microgravity together with radiation induced drop of survival fraction, proliferation inhibition, apoptosis, and DNA double-strand break formation of Beas-2B cells additively. They also additively induced Ras-related C3 botulinum toxin substrate 2 (RAC2) upregulation, leading to increased NADPH oxidase activity and increased intracellular reactive oxygen species (ROS) yield. The findings indicated that simulated microgravity and ionizing radiation presented an additive effect on cell death of human bronchial epithelial cells, which was mediated by RAC2 to some extent. The study provides a new perspective for the better understanding of the compound biological effects of the space environmental factors.

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