Epithelial Barrier Dysfunction in Chronic Respiratory Diseases

Carlier, François; Fays, Charlotte de; Pilette, Charles

doi:10.3389/fphys.2021.691227

Cited by 81 publications

(75 citation statements)

References 404 publications

(451 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The airway epithelium is composed of ciliated cells that are responsible for removing airborne pathogens and mucus away from lower airways and goblet cells that secrete mucus. In asthma and COPD, the airway epithelial barrier integrity is compromised with increased mucus production and accumulation, resulting in structural changes and airflow obstruction [ 55 , 56 ]. In addition to airway structure, the airway epithelium also contributes airway inflammation releasing pro-inflammatory cytokines such as TNFα and IL-33, which contribute to Th1 and Th2 inflammation, respectively [ 57 , 58 ].…”

Section: Corticosteroid Insensitivity In Asthma and Copd Pathophysiologymentioning

confidence: 99%

Oxidative Stress Promotes Corticosteroid Insensitivity in Asthma and COPD

et al. 2021

View full text Add to dashboard Cite

Corticosteroid insensitivity is a key characteristic of patients with severe asthma and COPD. These individuals experience greater pulmonary oxidative stress and inflammation, which contribute to diminished lung function and frequent exacerbations despite the often and prolonged use of systemic, high dose corticosteroids. Reactive oxygen and nitrogen species (RONS) promote corticosteroid insensitivity by disrupting glucocorticoid receptor (GR) signaling, leading to the sustained activation of pro-inflammatory pathways in immune and airway structural cells. Studies in asthma and COPD models suggest that corticosteroids need a balanced redox environment to be effective and to reduce airway inflammation. In this review, we discuss how oxidative stress contributes to corticosteroid insensitivity and the importance of optimizing endogenous antioxidant responses to enhance corticosteroid sensitivity. Future studies should aim to identify how antioxidant-based therapies can complement corticosteroids to reduce the need for prolonged high dose regimens in patients with severe asthma and COPD.

show abstract

Section: Corticosteroid Insensitivity In Asthma and Copd Pathophysiologymentioning

confidence: 99%

Oxidative Stress Promotes Corticosteroid Insensitivity in Asthma and COPD

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The airway epithelium is composed of five cell types including basal, goblet, ciliated, club, brush cells and cells of the diffuse neuroendocrine system ( Carlier et al, 2021 ) To determine whether our LGR5+ organoids cultured on day 12 formed a microarchitecture mimicking the nasal mucosa in vivo , we investigated their expression of functional molecules characteristic of nasal tissues using immunofluorescence, mRNA expression, western blot and FACS analysis. Firstly, we examined the expression of markers for goblet cells (Muc2), cilia (Tubulin) and apical junctional complexes (E-cadherin and ZO-1) by immunofluorescence.…”

Section: Resultsmentioning

confidence: 99%

Characterization of human nasal organoids from chronic rhinosinusitis patients

et al. 2022

View full text Add to dashboard Cite

Patient-derived organoids grown in three-dimensional cultures provide an excellent platform for phenotypic high-throughput screening and drug response research. Organoid technology has been applied to study stem cell biology and various human pathologies. This study investigates the characteristics and cellular morphology of organoids derived from primary human nasal epithelial cells (HNECs) of chronic rhinosinusitis (CRS) patients. Nasal organoids were cultured up to 20 days and morphological, cell composition, and functional parameters were measured by immunofluorescence, RT-qPCR, western-blot and FACS analysis. The results showed that nasal organoids expressed the stem cell marker Leucine Rich Repeat Containing G Protein-Coupled Receptor 5 (LGR5), and markers for apical junction genes, goblet cells and ciliated cells. Moreover, we were able to regrow and expand the nasal organoids well after freezing and thawing. This study promise an effective and feasible method for development of human nasal organoids, suitable for the phenotypic high-throughput screening and drug response research.

show abstract

“…The respiratory epithelium serves as the dominant barrier against P. aeruginosa invasion [16][17][18]. Intact epithelium has strictly controlled paracellular permeability due to the presence of intercellular junctions, primarily tight junction (TJs), and adherens junctions (AJs) [19,20].…”

Section: P Aeruginosa Regulation Of the Cytoskeletal Network In Lung Epithelial Cellsmentioning

confidence: 99%

The Role of Pseudomonas aeruginosa Virulence Factors in Cytoskeletal Dysregulation and Lung Barrier Dysfunction

Wagener

et al. 2021

Toxins

View full text Add to dashboard Cite

Pseudomonas (P.) aeruginosa is an opportunistic pathogen that causes serious infections and hospital-acquired pneumonia in immunocompromised patients. P. aeruginosa accounts for up to 20% of all cases of hospital-acquired pneumonia, with an attributable mortality rate of ~30–40%. The poor clinical outcome of P. aeruginosa-induced pneumonia is ascribed to its ability to disrupt lung barrier integrity, leading to the development of lung edema and bacteremia. Airway epithelial and endothelial cells are important architecture blocks that protect the lung from invading pathogens. P. aeruginosa produces a number of virulence factors that can modulate barrier function, directly or indirectly, through exploiting cytoskeleton networks and intercellular junctional complexes in eukaryotic cells. This review summarizes the current knowledge on P. aeruginosa virulence factors, their effects on the regulation of the cytoskeletal network and associated components, and molecular mechanisms regulating barrier function in airway epithelial and endothelial cells. A better understanding of these processes will help to lay the foundation for new therapeutic approaches against P. aeruginosa-induced pneumonia.

show abstract

Epithelial Barrier Dysfunction in Chronic Respiratory Diseases

Cited by 81 publications

References 404 publications

Oxidative Stress Promotes Corticosteroid Insensitivity in Asthma and COPD

Oxidative Stress Promotes Corticosteroid Insensitivity in Asthma and COPD

Characterization of human nasal organoids from chronic rhinosinusitis patients

The Role of Pseudomonas aeruginosa Virulence Factors in Cytoskeletal Dysregulation and Lung Barrier Dysfunction

Contact Info

Product

Resources

About