scholarly journals Ionocytes and CFTR Chloride Channel Expression in Normal and Cystic Fibrosis Nasal and Bronchial Epithelial Cells

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2090
Author(s):  
Paolo Scudieri ◽  
Ilaria Musante ◽  
Arianna Venturini ◽  
Daniela Guidone ◽  
Michele Genovese ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Chloride Channel ◽  
Ex Vivo ◽  
Chloride Secretion ◽  
Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Functional Studies ◽  
The Difference

The airway epithelium contains ionocytes, a rare cell type with high expression of Forkhead Box I1 (FOXI1) transcription factor and Cystic Fibrosis Transmembrane conductance Regulator (CFTR), a chloride channel that is defective in cystic fibrosis (CF). Our aim was to verify if ionocyte development is altered in CF and to investigate the relationship between ionocytes and CFTR-dependent chloride secretion. We collected nasal cells by brushing to determine ionocyte abundance. Nasal and bronchial cells were also expanded in vitro and reprogrammed to differentiated epithelia for morphological and functional studies. We found a relatively high (~3%) ionocyte abundance in ex vivo nasal samples, with no difference between CF and control individuals. In bronchi, ionocytes instead appeared very rarely as previously reported, thus suggesting a possible proximal–distal gradient in human airways. The difference between nasal and bronchial epithelial cells was maintained in culture, which suggests an epigenetic control of ionocyte development. In the differentiation phase of the culture procedure, we used two media that resulted in a different pattern of CFTR expression: confined to ionocytes or more broadly expressed. CFTR function was similar in both conditions, thus indicating that chloride secretion equally occurs irrespective of CFTR expression pattern.

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

Inhibition of chloride secretion in human bronchial epithelial cells by cigarette smoke extract

2005 ◽  
Vol 288 (5) ◽  
pp. L894-L902 ◽  
Author(s):  
James L. Kreindler ◽  
Alan D. Jackson ◽  
Philip A. Kemp ◽  
Robert J. Bridges ◽  
Henry Danahay
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Ion Transport ◽  
Cigarette Smoke ◽  
Apical Membrane ◽  
Chloride Secretion ◽  
Cigarette Smoke Extract ◽  
Bronchial Epithelial Cells ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial

Chronic bronchitis, a disease mainly of cigarette smokers, shares many clinical features with cystic fibrosis, a disease of altered ion transport, suggesting that the negative effects of cigarette smoke on mucociliary clearance may be mediated through alterations in ion transport. We tested the hypothesis that cigarette smoke extract would inhibit chloride secretion in human bronchial epithelial cells. In agreement with studies in canine trachea, cigarette smoke extract inhibited net chloride secretion without affecting sodium transport. We performed microelectrode impalements and impedance analysis studies to investigate the physiological mechanisms of this inhibition. These data demonstrated that cigarette smoke extract caused an acute increase in membrane resistances in conjunction with apical membrane hyperpolarization, an effect consistent with inhibition of an apical membrane anion conductance. After this acute phase, both membrane resistances decreased while membrane potentials continued to hyperpolarize, indicating that cigarette smoke extract also inhibited the basolateral entry of chloride into the cell. Furthermore, cigarette smoke extract caused an increase in mucin secretion. Therefore, the ion transport phenotype of human bronchial epithelial cells exposed to cigarette smoke extract is similar to that of cystic fibrosis epithelia in which there is sodium absorption out of proportion to chloride secretion in the setting of increased mucus secretion.

scholarly journals Bronchial epithelium in children: a key player in asthma

2016 ◽  
Vol 25 (140) ◽  
pp. 158-169 ◽  
Author(s):  
Ania Carsin ◽  
Julie Mazenq ◽  
Alexandra Ilstad ◽  
Jean-Christophe Dubus ◽  
Pascal Chanez ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Inflammation ◽  
Ex Vivo ◽  
Bronchial Epithelium ◽  
Bronchial Epithelial Cells ◽  
Physical Barrier ◽  
Bronchial Epithelial ◽  
Immunological Properties ◽  
Physical Chemical

Bronchial epithelium is a key element of the respiratory airways. It constitutes the interface between the environment and the host. It is a physical barrier with many chemical and immunological properties. The bronchial epithelium is abnormal in asthma, even in children. It represents a key component promoting airway inflammation and remodelling that can lead to chronic symptoms. In this review, we present an overview of bronchial epithelium and how to study it, with a specific focus on children. We report physical, chemical and immunological properties fromex vivoandin vitrostudies. The responses to various deleterious agents, such as viruses or allergens, may lead to persistent abnormalities orchestrated by bronchial epithelial cells. As epithelium dysfunctions occur early in asthma, reprogramming the epithelium may represent an ambitious goal to induce asthma remission in children.

scholarly journals Transforming Growth Factor-β1 Selectively Recruits microRNAs to the RNA-Induced Silencing Complex and Degrades CFTR mRNA under Permissive Conditions in Human Bronchial Epithelial Cells

2019 ◽  
Vol 20 (19) ◽  
pp. 4933 ◽  
Author(s):  
Nilay Mitash ◽  
Fangping Mu ◽  
Joshua E. Donovan ◽  
Michael M. Myerburg ◽  
Sarangarajan Ranganathan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Bronchial Epithelial Cells ◽  
Common Mutation ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Cftr Protein

<p>Mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (<italic>CFTR</italic>) gene lead to cystic fibrosis (CF). The most common mutation F508del inhibits folding and processing of CFTR protein. FDA-approved correctors rescue the biosynthetic processing of F508del-CFTR protein, while potentiators improve the rescued CFTR channel function. Transforming growth factor (TGF-&#x3B2;1), overexpressed in many CF patients, blocks corrector/potentiator rescue by inhibiting CFTR mRNA in vitro. Increased TGF-&#x3B2;1 signaling and acquired CFTR dysfunction are present in other lung diseases. To study the mechanism of TGF-&#x3B2;1 repression of CFTR, we used molecular, biochemical, and functional approaches in primary human bronchial epithelial cells from over 50 donors. TGF-&#x3B2;1 destabilized CFTR mRNA in cells from lungs with chronic disease, including CF, and impaired F508del-CFTR rescue by new-generation correctors. TGF-&#x3B2;1 increased the active pool of selected micro(mi)RNAs validated as CFTR inhibitors, recruiting them to the RNA-induced silencing complex (RISC). Expression of F508del-CFTR globally modulated TGF-&#x3B2;1-induced changes in the miRNA landscape, creating a permissive environment required for degradation of F508del-CFTR mRNA. In conclusion, TGF-&#x3B2;1 may impede the full benefit of corrector/potentiator therapy in CF patients. Studying miRNA recruitment to RISC under disease-specific conditions may help to better characterize the miRNAs utilized by TGF-&#x3B2;1 to destabilize CFTR mRNA.

scholarly journals Lung macrophages drive mucus production and steroid-resistant inflammation in chronic bronchitis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kristina Andelid ◽  
Karolina Öst ◽  
Anders Andersson ◽  
Esha Mohamed ◽  
Zala Jevnikar ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Chronic Bronchitis ◽  
Cross Talk ◽  
Alveolar Macrophages ◽  
Ex Vivo ◽  
Bronchial Epithelial Cells ◽  
Steroid Resistance ◽  
Bronchial Epithelial ◽  
Steroid Resistant ◽  
Copd Patients

Abstract Background Patients with chronic obstructive pulmonary disease (COPD) frequently suffer from chronic bronchitis (CB) and display steroid-resistant inflammation with increased sputum neutrophils and macrophages. Recently, a causal link between mucus hyper-concentration and disease progression of CB has been suggested. Methods In this study, we have evaluated the steroid sensitivity of purified, patient-derived sputum and alveolar macrophages and used a novel mechanistic cross-talk assay to examine how macrophages and bronchial epithelial cells cross-talk to regulate MUC5B production. Results We demonstrate that sputum plug macrophages isolated from COPD patients with chronic bronchitis (COPD/CB) are chronically activated and only partially respond to ex vivo corticosteroid treatment compared to alveolar macrophages isolated from lung resections. Further, we show that pseudo-stratified bronchial epithelial cells grown in air–liquid-interface are inert to direct bacterial lipopolysaccharide stimulation and that macrophages are able to relay this signal and activate the CREB/AP-1 transcription factor complex and subsequent MUC5B expression in epithelial cells through a soluble mediator. Using recombinant protein and neutralizing antibodies, we identified a key role for TNFα in this cross-talk. Conclusions For the first time, we describe ex vivo pharmacology in purified human sputum macrophages isolated from chronic bronchitis COPD patients and identify a possible basis for the steroid resistance frequently seen in this population. Our data pinpoint a critical role for chronically activated sputum macrophages in perpetuating TNFα-dependent signals driving mucus hyper-production. Targeting the chronically activated mucus plug macrophage phenotype and interfering with aberrant macrophage-epithelial cross-talk may provide a novel strategy to resolve chronic inflammatory lung disease.

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