scholarly journals Impaired Airway Epithelial Barrier Integrity in Response to Stenotrophomonas maltophilia Proteases, Novel Insights Using Cystic Fibrosis Bronchial Epithelial Cell Secretomics

2020 ◽  
Vol 11 ◽  
Author(s):  
Kevin Molloy ◽  
Gerard Cagney ◽  
Eugene T. Dillon ◽  
Kieran Wynne ◽  
Catherine M. Greene ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cell ◽  
Stenotrophomonas Maltophilia ◽  
Bronchial Epithelial Cell ◽  
Epithelial Barrier ◽  
Airway Epithelial ◽  
Bronchial Epithelial ◽  
Barrier Integrity

scholarly journals Lipoxin A4prevents tight junction disruption and delays the colonization of cystic fibrosis bronchial epithelial cells byPseudomonas aeruginosa

2016 ◽  
Vol 310 (11) ◽  
pp. L1053-L1061 ◽  
Author(s):  
Gerard Higgins ◽  
Coral Fustero Torre ◽  
Jean Tyrrell ◽  
Paul McNally ◽  
Brian J. Harvey ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Tight Junction ◽  
Cell Lines ◽  
Bronchial Epithelial Cell ◽  
Bacterial Invasion ◽  
Airway Epithelial ◽  
Bronchial Epithelial ◽  
Tight Junction Disruption

The specialized proresolution lipid mediator lipoxin A4(LXA4) is abnormally produced in cystic fibrosis (CF) airways. LXA4increases the CF airway surface liquid height and stimulates airway epithelial repair and tight junction formation. We report here a protective effect of LXA4(1 nM) against tight junction disruption caused by Pseudomonas aeruginosa bacterial challenge together with a delaying action against bacterial invasion in CF airway epithelial cells from patients with CF and immortalized cell lines. Bacterial invasion and tight junction integrity were measured by gentamicin exclusion assays and confocal fluorescence microscopy in non-CF (NuLi-1) and CF (CuFi-1) bronchial epithelial cell lines and in primary CF cultures, grown under an air/liquid interface, exposed to either a clinical or laboratory strains of P. aeruginosa. LXA4delayed P. aeruginosa invasion and transepithelial migration in CF and normal bronchial epithelial cell cultures. These protective effects of LXA4were inhibited by the ALX/FPR2 lipoxin receptor antagonist BOC-2. LXA4prevented the reduction in mRNA biosynthesis and protein abundance of the tight junction protein ZO-1 and reduced tight junction disruption induced by P. aeruginsosa inoculation. In conclusion, LXA4plays a protective role in bronchial epithelium by stimulating tight junction repair and by delaying and reducing the invasion of CF bronchial epithelial cells by P. aeruginsosa.

scholarly journals LIF Upregulates Expression of NK-1R in NHBE Cells

2006 ◽  
Vol 2006 ◽  
pp. 1-8 ◽  
Author(s):  
Cheng-Ping Hu ◽  
Jun-Tao Feng ◽  
Yu-Ling Tang ◽  
Jin-Qi Zhu ◽  
Min-Juan Lin ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Mek Inhibitor ◽  
Bronchial Epithelial Cell ◽  
Erk Pathway ◽  
Airway Epithelial ◽  
Bronchial Epithelial ◽  
Jak2 Inhibitor ◽  
Neurokinin 1 ◽  
Immunohistochemistry Stain ◽  
Stat Pathway

Leukemia inhibitory factor (LIF), a cytokine at the interface between neurobiology and immunology, is mainly mediated through JAK/STAT pathway and MAPK/ERK pathway. Evidence suggested LIF is related to the higher expression of neurokinin-1 receptor (NK-1R) in asthma. In this study, the immunohistochemistry stain showed the expressions of NK-1R, LIF, p-STAT3, and p-ERK1/2 in the lung tissues of allergic rats were increased compared with the controls, and the main positive cell type was airway epithelial cell. Normal human bronchial epithelial cells were treated with LIF in the presence or absence of AG490 (JAK2 inhibitor), PD98059 (MEK inhibitor), and the siRNA against STAT3. Western blot and RT-PCR indicated that LIF induced the expression of NK-1R, which was inhibited by the inhibitors mentioned above. No significant interaction was found between JAK/STAT pathway and MAPK/ERK pathway. In summary, bronchial epithelial cell changes in asthma are induced by LIF which promotes the expression of NK-1R, and JAK/STAT pathway and MAPK/ERK pathway may participate in this process.

Glucocorticoid regulation of GM-CSF: evidence for transcriptional mechanisms in airway epithelial cells

1998 ◽  
Vol 275 (2) ◽  
pp. L372-L378 ◽  
Author(s):  
Karissa K. Adkins ◽  
Tricia D. Levan ◽  
Roger L. Miesfeld ◽  
John W. Bloom
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Line ◽  
Bronchial Epithelial Cell ◽  
Airway Epithelial Cells ◽  
Epithelial Cell Line ◽  
Airway Epithelial ◽  
Dexamethasone Treatment ◽  
Bronchial Epithelial ◽  
Gm Csf

Inflammation plays a central role in the pathogenesis of asthma. Glucocorticoids are first-line anti-inflammatory therapy in the treatment of asthma and are effective inhibitors of inflammatory cytokines. Clinical data demonstrate that granulocyte-macrophage colony-stimulating factor (GM-CSF) production by airway epithelial cells may be an important target of inhaled glucocorticoid therapy. We examined the regulatory mechanisms of GM-CSF expression by interleukin-1β (IL-1β) and the synthetic glucocorticoid dexamethasone in the BEAS-2B human bronchial epithelial cell line. IL-1β stimulation resulted in a 15-fold induction of GM-CSF protein, which was associated with a corresponding 47-fold maximal induction of GM-CSF mRNA levels. Treatment with the transcriptional inhibitor actinomycin D before IL-1β stimulation completely abolished induction of GM-CSF mRNA, whereas incubation with cycloheximide had no effect. Taken together, these data demonstrate that IL-1β induction of GM-CSF is mediated through transcriptional mechanisms. Dexamethasone treatment of BEAS-2B cells produced an 80% inhibition of IL-1β-induced GM-CSF protein and a 51% inhibition of GM-CSF mRNA. GM-CSF mRNA was rapidly degraded in these cells, and dexamethasone treatment did not significantly affect this decay rate. We conclude that, in the BEAS-2B bronchial epithelial cell line, IL-1β induction and dexamethasone repression of GM-CSF expression are mediated predominantly through transcriptional mechanisms.

scholarly journals Exposure Effects Beyond the Epithelial Barrier: Transepithelial Induction of Oxidative Stress by Diesel Exhaust Particulates in Lung Fibroblasts in an Organotypic Human Airway Model

2020 ◽  
Vol 177 (1) ◽  
pp. 140-155
Author(s):  
Samantha C Faber ◽  
Nicole A McNabb ◽  
Pablo Ariel ◽  
Emily R Aungst ◽  
Shaun D McCullough
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cell ◽  
Adverse Effects ◽  
Diesel Exhaust ◽  
Bronchial Epithelial Cell ◽  
Human Bronchial Epithelial Cell ◽  
Lung Fibroblasts ◽  
Epithelial Barrier ◽  
Bronchial Epithelial

Abstract In vitro bronchial epithelial monoculture models have been pivotal in defining the adverse effects of inhaled toxicant exposures; however, they are only representative of one cellular compartment and may not accurately reflect the effects of exposures on other cell types. Lung fibroblasts exist immediately beneath the bronchial epithelial barrier and play a central role in lung structure and function, as well as disease development and progression. We tested the hypothesis that in vitro exposure of a human bronchial epithelial cell barrier to the model oxidant diesel exhaust particulates caused transepithelial oxidative stress in the underlying lung fibroblasts using a human bronchial epithelial cell and lung fibroblast coculture model. We observed that diesel exhaust particulates caused transepithelial oxidative stress in underlying lung fibroblasts as indicated by intracellular accumulation of the reactive oxygen species hydrogen peroxide, oxidation of the cellular antioxidant glutathione, activation of NRF2, and induction of oxidative stress-responsive genes. Further, targeted antioxidant treatment of lung fibroblasts partially mitigated the oxidative stress response gene expression in adjacent human bronchial epithelial cells during diesel exhaust particulate exposure. This indicates that exposure-induced oxidative stress in the airway extends beyond the bronchial epithelial barrier and that lung fibroblasts are both a target and a mediator of the adverse effects of inhaled chemical exposures despite being separated from the inhaled material by an epithelial barrier. These findings illustrate the value of coculture models and suggest that transepithelial exposure effects should be considered in inhalation toxicology research and testing.

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