scholarly journals Restoration of Chloride Efflux by Azithromycin in Airway Epithelial Cells of Cystic Fibrosis Patients

2011 ◽  
Vol 55 (4) ◽  
pp. 1792-1793 ◽  
Author(s):  
Vinciane Saint-Criq ◽  
Carine Rebeyrol ◽  
Manon Ruffin ◽  
Telma Roque ◽  
Loïc Guillot ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Airway Epithelial Cells ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Respiratory Condition ◽  
Beneficial Effects ◽  
Chronic Obstructive Pulmonary Diseases ◽  
Anti Inflammatory ◽  
Inflammatory Effect ◽  
Airway Cells

ABSTRACTAzithromycin (AZM) has shown promising anti-inflammatory properties in chronic obstructive pulmonary diseases, and clinical studies have presented an improvement in the respiratory condition of cystic fibrosis (CF) patients. The aim of this study was to investigate, in human airway cells, the mechanism by which AZM has beneficial effects in CF. We demonstrated that AZM did not have any anti-inflammatory effect on CF airway cells but restored Cl−efflux.

scholarly journals Insulin signaling via the PI3-kinase/Akt pathway regulates airway glucose uptake and barrier function in a CFTR-dependent manner

2017 ◽  
Vol 312 (5) ◽  
pp. L688-L702 ◽  
Author(s):  
Samuel A. Molina ◽  
Hannah K. Moriarty ◽  
Daniel T. Infield ◽  
Barry R. Imhoff ◽  
Rachel J. Vance ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Small Molecules ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Airway Epithelia ◽  
Human Airway ◽  
Airway Cells

Cystic fibrosis-related diabetes is the most common comorbidity associated with cystic fibrosis (CF) and correlates with increased rates of lung function decline. Because glucose is a nutrient present in the airways of patients with bacterial airway infections and because insulin controls glucose metabolism, the effect of insulin on CF airway epithelia was investigated to determine the role of insulin receptors and glucose transport in regulating glucose availability in the airway. The response to insulin by human airway epithelial cells was characterized by quantitative PCR, immunoblot, immunofluorescence, and glucose uptake assays. Phosphatidylinositol 3-kinase/protein kinase B (Akt) signaling and cystic fibrosis transmembrane conductance regulator (CFTR) activity were analyzed by pharmacological and immunoblot assays. We found that normal human primary airway epithelial cells expressed glucose transporter 4 and that application of insulin stimulated cytochalasin B-inhibitable glucose uptake, consistent with a requirement for glucose transporter translocation. Application of insulin to normal primary human airway epithelial cells promoted airway barrier function as demonstrated by increased transepithelial electrical resistance and decreased paracellular flux of small molecules. This provides the first demonstration that airway cells express insulin-regulated glucose transporters that act in concert with tight junctions to form an airway glucose barrier. However, insulin failed to increase glucose uptake or decrease paracellular flux of small molecules in human airway epithelia expressing F508del-CFTR. Insulin stimulation of Akt1 and Akt2 signaling in CF airway cells was diminished compared with that observed in airway cells expressing wild-type CFTR. These results indicate that the airway glucose barrier is regulated by insulin and is dysfunctional in CF.

scholarly journals Dysfunctional Inflammation in Cystic Fibrosis Airways: From Mechanisms to Novel Therapeutic Approaches

2021 ◽  
Vol 22 (4) ◽  
pp. 1952
Author(s):  
Alessandra Ghigo ◽  
Giulia Prono ◽  
Elisa Riccardi ◽  
Virginia De Rose
Keyword(s):  
Cystic Fibrosis ◽  
Critical Role ◽  
Airway Epithelial Cells ◽  
Lung Damage ◽  
Molecular Defect ◽  
Apical Surface ◽  
Therapeutic Approaches ◽  
Beneficial Effects ◽  
Anti Inflammatory ◽  
Novel Therapeutic

Cystic fibrosis (CF) is an inherited disorder caused by mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, an ATP-gated chloride channel expressed on the apical surface of airway epithelial cells. CFTR absence/dysfunction results in defective ion transport and subsequent airway surface liquid dehydration that severely compromise the airway microenvironment. Noxious agents and pathogens are entrapped inside the abnormally thick mucus layer and establish a highly inflammatory environment, ultimately leading to lung damage. Since chronic airway inflammation plays a crucial role in CF pathophysiology, several studies have investigated the mechanisms responsible for the altered inflammatory/immune response that, in turn, exacerbates the epithelial dysfunction and infection susceptibility in CF patients. In this review, we address the evidence for a critical role of dysfunctional inflammation in lung damage in CF and discuss current therapeutic approaches targeting this condition, as well as potential new treatments that have been developed recently. Traditional therapeutic strategies have shown several limitations and limited clinical benefits. Therefore, many efforts have been made to develop alternative treatments and novel therapeutic approaches, and recent findings have identified new molecules as potential anti-inflammatory agents that may exert beneficial effects in CF patients. Furthermore, the potential anti-inflammatory properties of CFTR modulators, a class of drugs that directly target the molecular defect of CF, also will be critically reviewed. Finally, we also will discuss the possible impact of SARS-CoV-2 infection on CF patients, with a major focus on the consequences that the viral infection could have on the persistent inflammation in these patients.

Synthesis and anti-inflammatory effect of lipoxins in human airway epithelial cells

2007 ◽  
Vol 61 (5) ◽  
pp. 261-267 ◽  
Author(s):  
Caroline Bonnans ◽  
Delphine Gras ◽  
Claude Chavis ◽  
Brigitte Mainprice ◽  
Isabelle Vachier ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Human Airway ◽  
Anti Inflammatory ◽  
Inflammatory Effect ◽  
Human Airway Epithelial Cells

scholarly journals Airway Epithelium Dysfunction in Cystic Fibrosis and COPD

2018 ◽  
Vol 2018 ◽  
pp. 1-20 ◽  
Author(s):  
Virginia De Rose ◽  
Kevin Molloy ◽  
Sophie Gohy ◽  
Charles Pilette ◽  
Catherine M. Greene
Keyword(s):  
Cystic Fibrosis ◽  
Airway Epithelium ◽  
Critical Role ◽  
Airflow Obstruction ◽  
Alveolar Epithelium ◽  
Airway Epithelial Cells ◽  
Lung Damage ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Epithelial Dysfunction

Cystic fibrosis is a genetic disease caused by mutations in the CFTR gene, whereas chronic obstructive pulmonary disease (COPD) is mainly caused by environmental factors (mostly cigarette smoking) on a genetically susceptible background. Although the etiology and pathogenesis of these diseases are different, both are associated with progressive airflow obstruction, airway neutrophilic inflammation, and recurrent exacerbations, suggesting common mechanisms. The airway epithelium plays a crucial role in maintaining normal airway functions. Major molecular and morphologic changes occur in the airway epithelium in both CF and COPD, and growing evidence suggests that airway epithelial dysfunction is involved in disease initiation and progression in both diseases. Structural and functional abnormalities in both airway and alveolar epithelium have a relevant impact on alteration of host defences, immune/inflammatory response, and the repair process leading to progressive lung damage and impaired lung function. In this review, we address the evidence for a critical role of dysfunctional airway epithelial cells in chronic airway inflammation and remodelling in CF and COPD, highlighting the common mechanisms involved in the epithelial dysfunction as well as the similarities and differences of the two diseases.

Anti-inflammatory effects of azithromycin in cystic fibrosis airway epithelial cells

2006 ◽  
Vol 350 (4) ◽  
pp. 977-982 ◽  
Author(s):  
Cristina Cigana ◽  
Elena Nicolis ◽  
Matteo Pasetto ◽  
Baroukh Maurice Assael ◽  
Paola Melotti
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Cystic Fibrosis Airway ◽  
Anti Inflammatory
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