scholarly journals Cystic Fibrosis Clinical Isolates of Aspergillus fumigatus Induce Similar Muco-inflammatory Responses in Primary Airway Epithelial Cells

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1020
Author(s):  
Samantha A. McLean ◽  
Leilani Cullen ◽  
Dianne J. Gardam ◽  
Craig J. Schofield ◽  
Daniel R. Laucirica ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Aspergillus Fumigatus ◽  
Inflammatory Responses ◽  
Antifungal Susceptibility ◽  
Airway Epithelial Cells ◽  
Clinical Isolates ◽  
Airway Epithelial ◽  
Mucus Production ◽  
Or Gene ◽  
Epithelial Inflammation

Aspergillus is increasingly associated with lung inflammation and mucus plugging in early cystic fibrosis (CF) disease during which conidia burden is low and strains appear to be highly diverse. It is unknown whether clinical Aspergillus strains vary in their capacity to induce epithelial inflammation and mucus production. We tested the hypothesis that individual colonising strains of Aspergillus fumigatus would induce different responses. Ten paediatric CF Aspergillus isolates were compared along with two systemically invasive clinical isolates and an ATCC reference strain. Isolates were first characterised by ITS gene sequencing and screened for antifungal susceptibility. Three clusters (A−C) of Aspergillus isolates were identified by ITS. Antifungal susceptibility was variable, particularly for itraconazole. Submerged CF and non-CF monolayers as well as differentiated primary airway epithelial cell cultures were incubated with conidia for 24 h to allow germination. None of the clinical isolates were found to significantly differ from one another in either IL-6 or IL-8 release or gene expression of secretory mucins. Clinical Aspergillus isolates appear to be largely homogenous in their mucostimulatory and immunostimulatory capacities and, therefore, only the antifungal resistance characteristics are likely to be clinically important.

Innate Inflammatory Responses of Pediatric Cystic Fibrosis Airway Epithelial Cells

2011 ◽  
Vol 44 (6) ◽  
pp. 761-767 ◽  
Author(s):  
Erika N. Sutanto ◽  
Anthony Kicic ◽  
Clara J. Foo ◽  
Paul T. Stevens ◽  
David Mullane ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Inflammatory Responses ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Cystic Fibrosis Airway

Oxidative stress modulates the expression of genes involved in cell survival in ΔF508 cystic fibrosis airway epithelial cells

2014 ◽  
Vol 46 (17) ◽  
pp. 634-646 ◽  
Author(s):  
Grégory Voisin ◽  
Guillaume F. Bouvet ◽  
Pierre Legendre ◽  
André Dagenais ◽  
Chantal Massé ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Cell Survival ◽  
Cell Lines ◽  
Inflammatory Responses ◽  
Airway Epithelial Cells ◽  
Gene Profiling ◽  
Airway Epithelial ◽  
Transcriptomic Response

Although cystic fibrosis (CF) pathophysiology is explained by a defect in CF transmembrane conductance regulator (CFTR) protein, the broad spectrum of disease severity is the consequence of environmental and genetic factors. Among them, oxidative stress has been demonstrated to play an important role in the evolution of this disease, with susceptibility to oxidative damage, decline of pulmonary function, and impaired lung antioxidant defense. Although oxidative stress has been implicated in the regulation of inflammation, its molecular outcomes in CF cells remain to be evaluated. To address the question, we compared the gene expression profile in NuLi-1 cells with wild-type CFTR and CuFi-1 cells homozygous for ΔF508 mutation cultured at air-liquid interface. We analyzed the transcriptomic response of these cell lines with microarray technology, under basal culture conditions and after 24 h oxidative stress induced by 15 μM 2,3-dimethoxy-1,4-naphtoquinone. In the absence of oxidative conditions, CuFi-1 gene profiling showed typical dysregulated inflammatory responses compared with NuLi-1. In the presence of oxidative conditions, the transcriptome of CuFi-1 cells reflected apoptotic transcript modulation. These results were confirmed in the CFBE41o- and corrCFBE41o- cell lines as well as in primary culture of human CF airway epithelial cells. Altogether, our data point to the influence of oxidative stress on cell survival functions in CF and identify several genes that could be implicated in the inflammation response observed in CF patients.

Differential expression of ORCC and CFTR induced by low temperature in CF airway epithelial cells

1995 ◽  
Vol 268 (1) ◽  
pp. C243-C251 ◽  
Author(s):  
M. E. Egan ◽  
E. M. Schwiebert ◽  
W. B. Guggino
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Incubation Temperature ◽  
Cell Types ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Channel Activity ◽  
Patch Clamp Recording ◽  
Cl Channel ◽  
Channel Expression

When nonepithelial cell types expressing the delta F508-cystic fibrosis transmembrane conductance regulator (CFTR) mutation are grown at reduced temperatures, the mutant protein can be properly processed. The effect of low temperatures on Cl- channel activity in airway epithelial cells that endogenously express the delta F508-CFTR mutation has not been investigated. Therefore, we examined the effect of incubation temperature on both CFTR and outwardly rectifying Cl- channel (ORCC) activity in normal, in cystic fibrosis (CF)-affected, and in wild-type CFTR-complemented CF airway epithelia with use of a combination of inside-out and whole cell patch-clamp recording, 36Cl- efflux assays, and immunocytochemistry. We report that incubation of CF-affected airway epithelial cells at 25-27 degrees C is associated with the appearance of a protein kinase A-stimulated CFTR-like Cl- conductance. In addition to the appearance of CFTR Cl- channel activity, there is, however, a decrease in the number of active ORCC when cells are grown at 25-27 degrees C, suggesting that the decrease in incubation temperature may be associated with multiple alterations in ion channel expression and/or regulation in airway epithelial cells.

Basal chloride currents in murine airway epithelial cells: modulation by CFTR

1998 ◽  
Vol 274 (4) ◽  
pp. C904-C913 ◽  
Author(s):  
R. Tarran ◽  
M. A. Gray ◽  
M. J. Evans ◽  
W. H. Colledge ◽  
R. Ratcliff ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Airway Epithelial Cells ◽  
Transmembrane Conductance Regulator ◽  
Airway Epithelial ◽  
Wild Type ◽  
Patch Clamp Technique ◽  
Chloride Currents ◽  
Cation Permeability ◽  
Current Voltage ◽  
Respiratory Cells

We have isolated ciliated respiratory cells from the nasal epithelium of wild-type and cystic fibrosis (CF) null mice and used the patch-clamp technique to investigate their basal conductances. Current-clamp experiments on unstimulated cells indicated the presence of K+ and Cl− conductances and, under certain conditions, a small Na+conductance. Voltage-clamp experiments revealed three distinct Cl− conductances. I tv-indep was time and voltage independent with a linear current-voltage ( I- V) plot; I v-actexhibited activation at potentials greater than ±50 mV, giving an S-shaped I- Vplot; and I hyp-act was activated by hyperpolarizing potentials and had an inwardly rectified I- Vplot. The current density sequence was I hyp-act = I v-act ≫ I tv-indep. These conductances had Cl−-to- N-methyl-d-glucamine cation permeability ratios of between 2.8 and 10.3 and were unaffected by tamoxifen, flufenamate, glibenclamide, DIDS, and 5-nitro-2-(3-phenylpropylamino) benzoic acid but were inhibited by Zn2+ and Gd3+. I tv-indep and I v-act were present in wild-type and CF cells at equal density and frequency. However, I hyp-actwas detected in only 3% of CF cells compared with 26% of wild-type cells, suggesting that this conductance may be modulated by cystic fibrosis transmembrane conductance regulator (CFTR).

scholarly journals Overproduction of growth differentiation factor 15 promotes human rhinovirus infection and virus-induced inflammation in the lung

2018 ◽  
Vol 314 (3) ◽  
pp. L514-L527 ◽  
Author(s):  
Qun Wu ◽  
Di Jiang ◽  
Niccolette R. Schaefer ◽  
Laura Harmacek ◽  
Brian P. O’Connor ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Responses ◽  
Airway Epithelial Cells ◽  
Human Rhinovirus ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Growth Differentiation Factor 15 ◽  
Human Airway ◽  
Differentiation Factor ◽  
Human Airway Epithelial Cells

Human rhinovirus (HRV) is the most common virus contributing to acute exacerbations of chronic obstructive pulmonary disease (COPD) nearly year round, but the mechanisms have not been well elucidated. Recent clinical studies suggest that high levels of growth differentiation factor 15 (GDF15) protein in the blood are associated with an increased yearly rate of all-cause COPD exacerbations. Therefore, in the current study, we investigated whether GDF15 promotes HRV infection and virus-induced lung inflammation. We first examined the role of GDF15 in regulating host defense and HRV-induced inflammation using human GDF15 transgenic mice and cultured human GDF15 transgenic mouse tracheal epithelial cells. Next, we determined the effect of GDF15 on viral replication, antiviral responses, and inflammation in human airway epithelial cells with GDF15 knockdown and HRV infection. Finally, we explored the signaling pathways involved in airway epithelial responses to HRV infection in the context of GDF15. Human GDF15 protein overexpression in mice led to exaggerated inflammatory responses to HRV, increased infectious particle release, and decreased IFN-λ2/3 (IL-28A/B) mRNA expression in the lung. Moreover, GDF15 facilitated HRV replication and inflammation via inhibiting IFN-λ1/IL-29 protein production in human airway epithelial cells. Lastly, Smad1 cooperated with interferon regulatory factor 7 (IRF7) to regulate airway epithelial responses to HRV infection partly via GDF15 signaling. Our results reveal a novel function of GDF15 in promoting lung HRV infection and virus-induced inflammation, which may be a new mechanism for the increased susceptibility and severity of respiratory viral (i.e., HRV) infection in cigarette smoke-exposed airways with GDF15 overproduction.

Glutathione permeability of CFTR

1998 ◽  
Vol 275 (1) ◽  
pp. C323-C326 ◽  
Author(s):  
Paul Linsdell ◽  
John W. Hanrahan
Keyword(s):  
Oxidative Stress ◽  
Cystic Fibrosis ◽  
Ion Channel ◽  
Airway Epithelial Cells ◽  
Transmembrane Conductance Regulator ◽  
Airway Epithelial ◽  
Transmembrane Conductance ◽  
High Concentrations ◽  
Cystic Fibrosis Transmembrane ◽  
Glutathione Transport

The cystic fibrosis transmembrane conductance regulator (CFTR) forms an ion channel that is permeable both to Cl− and to larger organic anions. Here we show, using macroscopic current recording from excised membrane patches, that the anionic antioxidant tripeptide glutathione is permeant in the CFTR channel. This permeability may account for the high concentrations of glutathione that have been measured in the surface fluid that coats airway epithelial cells. Furthermore, loss of this pathway for glutathione transport may contribute to the reduced levels of glutathione observed in airway surface fluid of cystic fibrosis patients, which has been suggested to contribute to the oxidative stress observed in the lung in cystic fibrosis. We suggest that release of glutathione into airway surface fluid may be a novel function of CFTR.

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