Extent of Rescue of F508del-CFTR Function by VX-809 and VX-770 in Human Nasal Epithelial Cells Correlates with SNP rs7512462 in SLC26A9 Gene in F508del/F508del Cystic Fibrosis Patients

2018 ◽  
Author(s):  
Arthur Kmit ◽  
Fernando Augusto de Lima Marson ◽  
Stéphanie Villa-Nova Pereira ◽  
Adriana Mendes Vinagre ◽  
Gabriela Silva Leite ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Nasal Epithelial Cells ◽  
Human Nasal Epithelial Cells

Macrolide Treatment Decreased the Size of Nasal Polyps and IL-8 Levels in Nasal Lavage

2000 ◽  
Vol 14 (3) ◽  
pp. 143-148 ◽  
Author(s):  
Takechiyo Yamada ◽  
Shigeharu Fujieda ◽  
Shigehito Mori ◽  
Hideyuki Yamamoto ◽  
Hitoshi Saito
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Experimental Studies ◽  
Nasal Lavage ◽  
Nasal Epithelial Cells ◽  
Diffuse Panbronchiolitis ◽  
Human Nasal Epithelial Cells

Recently, epidemiologic and experimental studies have been reported that long-term macrolides are effective for the treatment of chronic airway inflammatory diseases including diffuse panbronchiolitis, chronic rhinosinusitis, and cystic fibrosis (Jaffe A, Francis J, Rosenthal M, et al. Long-term azithromycin may improve lung function in children with cystic fibrosis. Lancet 351:420, 1998), and that macrolides can directly reduce the production of IL-8 by nasal epithelial cells (Suzuki H, Shimomura A, Ikeda K, et al. Inhibitory effect of macrolides on interleukin-8 secretion from cultured human nasal epithelial cells. Laryngoscope 107:1661–1666, 1997). In this study we administered macrolides with 14-membered rings to patients with nasal polyps due to chronic rhinosinusitis for at least 3 months and measured the IL-8 level in nasal lavage from those patients. The IL-8 levels in nasal lavage from patients with nasal polyps were reduced during macrolide treatment. There was significant correlation between decreased IL-8 levels in nasal lavage and the clinical effect of macrolides on the size of the nasal polyps. In the group whose polyps were reduced in size, the IL-8 levels dramatically decreased from 231.2 pg/mL to 44.0 pg/mL (p < 0.05), and were significantly higher before macrolide treatment than those in the group whose polyps showed no change (p < 0.005). This reduction in IL-8 may be an important aspect of the effect of macrolide treatment on nasal polyps in chronic rhinosinusitis.

Effects of various secretagogues on [Ca2+]i in cultured human nasal epithelial cells

1991 ◽  
Vol 69 (8) ◽  
pp. 1211-1216 ◽  
Author(s):  
Robert A. Harris ◽  
Kenneth G. Baimbridge ◽  
Michael A. Bridges ◽  
John E. Phillips
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Prostaglandin E ◽  
Epithelial Tissue ◽  
Nasal Epithelial Cells ◽  
Fura 2 ◽  
Culture Cells ◽  
Human Nasal Epithelial Cells ◽  
Messenger System ◽  
Electrolyte Secretion

Recent studies conducted on cultured canine tracheal cells have suggested that a complex relationship exists between cAMP and Ca2+ in the control of electrolyte secretion. The goal of this study was to determine if the Ca2+ second messenger system functions in a similar fashion in cultured human nasal epithelial cells, a tissue in which control of electrolyte secretion is known to be disrupted in the genetic disease, cystic fibrosis. Human nasal epithelial tissue was obtained as a by-product of surgery and put into monolayer cell culture. After 4–5 days in culture, cells were loaded with fura-2 and intracellular free Ca2+ measured as previously reported. We found that bradykinin increased intracellular free Ca2+ in all cells tested, whereas isoproterenol increased intracellular free Ca2+ in only half the cells tested, suggesting that more than one transporting cell type may be present in this tissue. Epinephrine and prostaglandin E2 had no effect on intracellular free Ca2+. We found that the voltage-sensitive Ca2+ channel blocker verapamil had no effect on the bradykinin-induced change in intracellular free Ca2+. Removal of Ca2+ from the bathing saline only slightly attenuated the increase in intracellular free Ca2+ that resulted from stimulation with bradykinin. We conclude that the source of the increased intracellular free CA2+, observed during stimulation with secretagogues, was primarily intracellular stores.Key words: airway epithelia, [Ca2+]i, calcium, bradykinin, cystic fibrosis, fura-2.

scholarly journals Extent of rescue of F508del-CFTR function by VX-809 and VX-770 in human nasal epithelial cells correlates with SNP rs7512462 in SLC26A9 gene in F508del/F508del Cystic Fibrosis patients

2019 ◽  
Vol 1865 (6) ◽  
pp. 1323-1331 ◽  
Author(s):  
Arthur Kmit ◽  
Fernando Augusto Lima Marson ◽  
Stéphanie Villa-Nova Pereira ◽  
Adriana Mendes Vinagre ◽  
Gabriela Silva Leite ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Nasal Epithelial Cells ◽  
Human Nasal Epithelial Cells

scholarly journals Berberine and Obatoclax Inhibit SARS-Cov-2 Replication in Primary Human Nasal Epithelial Cells In Vitro

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 282
Author(s):  
Finny S. Varghese ◽  
Esther van Woudenbergh ◽  
Gijs J. Overheul ◽  
Marc J. Eleveld ◽  
Lisa Kurver ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Early Stage ◽  
Antiviral Drugs ◽  
Target Cells ◽  
Nasal Epithelial Cells ◽  
Cytokines And Chemokines ◽  
Human Nasal Epithelial Cells ◽  
Apoptotic Protein ◽  
Air Liquid Interface

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a new human pathogen in late 2019 and it has infected over 100 million people in less than a year. There is a clear need for effective antiviral drugs to complement current preventive measures, including vaccines. In this study, we demonstrate that berberine and obatoclax, two broad-spectrum antiviral compounds, are effective against multiple isolates of SARS-CoV-2. Berberine, a plant-derived alkaloid, inhibited SARS-CoV-2 at low micromolar concentrations and obatoclax, which was originally developed as an anti-apoptotic protein antagonist, was effective at sub-micromolar concentrations. Time-of-addition studies indicated that berberine acts on the late stage of the viral life cycle. In agreement, berberine mildly affected viral RNA synthesis, but it strongly reduced infectious viral titers, leading to an increase in the particle-to-pfu ratio. In contrast, obatoclax acted at the early stage of the infection, which is in line with its activity to neutralize the acidic environment in endosomes. We assessed infection of primary human nasal epithelial cells that were cultured on an air-liquid interface and found that SARS-CoV-2 infection induced and repressed expression of specific sets of cytokines and chemokines. Moreover, both obatoclax and berberine inhibited SARS-CoV-2 replication in these primary target cells. We propose berberine and obatoclax as potential antiviral drugs against SARS-CoV-2 that could be considered for further efficacy testing.

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