Computational Analysis of RNA-Seq Data from Airway Epithelial Cells for Studying Lung Disease

2018 ◽  
pp. 203-235
Author(s):  
Nathan D. Jackson ◽  
Lando Ringel ◽  
Max A. Seibold
Keyword(s):  
Epithelial Cells ◽  
Lung Disease ◽  
Computational Analysis ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Rna Seq

Pseudomonaspyocyanine alters calcium signaling in human airway epithelial cells

1998 ◽  
Vol 274 (6) ◽  
pp. L893-L900 ◽  
Author(s):  
Gerene M. Denning ◽  
Michelle A. Railsback ◽  
George T. Rasmussen ◽  
Charles D. Cox ◽  
Bradley E. Britigan
Keyword(s):  
Epithelial Cells ◽  
Lung Disease ◽  
Cell Function ◽  
Oxidant Stress ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Human Airway ◽  
Human Airway Epithelial Cells

Pseudomonas aeruginosa, an opportunistic human pathogen, causes both acute and chronic lung disease. P. aeruginosa exerts many of its pathophysiological effects by secreting virulence factors, including pyocyanine, a redox-active compound that increases intracellular oxidant stress. Because oxidant stress has been shown to affect cytosolic Ca2+concentration ([Ca2+]c) in other cell types, we studied the effect of pyocyanine on [Ca2+]cin human airway epithelial cells (A549 and HBE). At lower concentrations, pyocyanine inhibits inositol 1,4,5-trisphosphate formation and [Ca2+]cincreases in response to G protein-coupled receptor agonists. Conversely, at higher concentrations, pyocyanine itself increases [Ca2+]c. The pyocyanine-dependent [Ca2+]cincrease appears to be oxidant dependent and to result from increased inositol trisphosphate and release of Ca2+from intracellular stores. Ca2+plays a central role in epithelial cell function, including regulation of ion transport, mucus secretion, and ciliary beat frequency. By disrupting Ca2+homeostasis, pyocyanine could interfere with these critical functions and contribute to the pathophysiological effects observed in Pseudomonas-associated lung disease.

scholarly journals Carcinogenic effects of oil dispersants: A KEGG pathway-based RNA-seq study of human airway epithelial cells

Gene ◽  
2017 ◽  
Vol 602 ◽  
pp. 16-23 ◽  
Author(s):  
Yao-Zhong Liu ◽  
Lei Zhang ◽  
Astrid M Roy-Engel ◽  
Shigeki Saito ◽  
Joseph A Lasky ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Kegg Pathway ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Rna Seq ◽  
Oil Dispersants ◽  
Human Airway ◽  
Carcinogenic Effects ◽  
Human Airway Epithelial Cells

scholarly journals IL-32 expression in the airway epithelial cells of patients with Mycobacterium avium complex lung disease

2011 ◽  
Vol 23 (11) ◽  
pp. 679-691 ◽  
Author(s):  
X. Bai ◽  
A. R. Ovrutsky ◽  
M. Kartalija ◽  
K. Chmura ◽  
A. Kamali ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Lung Disease ◽  
Mycobacterium Avium ◽  
Mycobacterium Avium Complex ◽  
Airway Epithelial Cells ◽  
Airway Epithelial

scholarly journals The impact of oil spill to lung health—Insights from an RNA-seq study of human airway epithelial cells

Gene ◽  
2016 ◽  
Vol 578 (1) ◽  
pp. 38-51 ◽  
Author(s):  
Yao-Zhong Liu ◽  
Astrid M. Roy-Engel ◽  
Melody C. Baddoo ◽  
Erik K. Flemington ◽  
Guangdi Wang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Oil Spill ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Rna Seq ◽  
Human Airway ◽  
Lung Health ◽  
The Impact ◽  
Human Airway Epithelial Cells

scholarly journals Increased susceptibility of cystic fibrosis airway epithelial cells to ferroptosis

2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Pramila Maniam ◽  
Ama-Tawiah Essilfie ◽  
Murugan Kalimutho ◽  
Dora Ling ◽  
David M. Frazer ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lipid Peroxidation ◽  
Cell Death ◽  
Epithelial Cells ◽  
Lung Disease ◽  
Ferrous Iron ◽  
Airway Epithelial Cells ◽  
Iron Accumulation ◽  
Airway Epithelial ◽  
Increased Susceptibility

Abstract Background Defective chloride transport in airway epithelial cells (AECs) and the associated lung disease are the main causes of morbidity and early mortality in cystic fibrosis (CF). Abnormal airway iron homeostasis and the presence of lipid peroxidation products, indicative of oxidative stress, are features of CF lung disease. Results Here, we report that CF AECs (IB3-1) are susceptible to ferroptosis, a type of cell death associated with iron accumulation and lipid peroxidation. Compared to isogenic CFTR corrected cells (C38), the IB3-1 cells showed increased susceptibility to cell death upon exposure to iron in the form of ferric ammonium citrate (FAC) and the ferroptosis inducer, erastin. This phenotype was accompanied by accumulation of intracellular ferrous iron and lipid peroxides and the extracellular release of malondialdehyde, all indicative of redox stress, and increased levels of lactate dehydrogenase in the culture supernatant, indicating enhanced cell injury. The ferric iron chelator deferoxamine (DFO) and the lipophilic antioxidant ferrostatin-1 inhibited FAC and erastin induced ferroptosis in IB3-1 cells. Glutathione peroxidase 4 (GPX4) expression was decreased in IB3-1 cells treated with FAC and erastin, but was unchanged in C38 AECs. Necroptosis appeared to be involved in the enhanced susceptibility of IB3-1 AECs to ferroptosis, as evidenced by partial cell death rescue with necroptosis inhibitors and enhanced mixed lineage kinase domain-like (MLKL) localisation to the plasma membrane. Conclusion These studies suggest that the increased susceptibility of CF AECs to ferroptosis is linked to abnormal intracellular ferrous iron accumulation and reduced antioxidant defences. In addition, the process of ferroptotic cell death in CF AECs does not appear to be a single entity and for the first time we describe necroptosis as a potential contributory factor. Iron chelation and antioxidant treatments may be promising therapeutic interventions in cystic fibrosis. Graphical Abstract

scholarly journals Corticosteroid-resistant inflammatory signalling in Pseudomonas-infected bronchial cells

2017 ◽  
Vol 3 (2) ◽  
pp. 00144-2016 ◽  
Author(s):  
Mirai Mizutani ◽  
Julie Bérubé ◽  
Heather G. Ahlgren ◽  
Joanie Bernier ◽  
Elias Matouk ◽  
...  
Keyword(s):  
Lung Function ◽  
Epithelial Cells ◽  
Inflammatory Response ◽  
Lung Disease ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Inflammatory Signalling ◽  
Microbiological Analyses

Decreasing the inflammatory response that leads to tissue damage during cystic fibrosis (CF) lung disease has been a long-standing goal of CF therapy. While corticosteroids are widely used anti-inflammatory drugs, their efficacy in CF lung disease remains debated. The complex interaction between the colonising bacteria and the host environment may impact corticosteroid responsiveness.In this study, sputum samples from adult CF patients were collected at baseline and during pulmonary exacerbation episodes. Lung function measurements and sputum microbiological analyses were performed. In parallel, the inflammatory response and corticosteroid sensitivity of airway epithelial cells to Pseudomonas-derived exoproducts was investigated.We report that adult CF patients colonised with mucoid Pseudomonas aeruginosa have higher levels of baseline inflammation, more frequent exacerbations and worse lung function compared with patients colonised with nonmucoid P. aeruginosa. Moreover, mucoid P. aeruginosa activates NF-κB via Toll-like receptor (TLR) 2, which acts in an additive manner to TLR5 to drive inflammation in airway epithelial cells. Furthermore, TLR2-mediated intracellular signalling is more resistant to the anti-inflammatory effects of corticosteroid when compared with other TLR signalling pathways.Overall, these results suggest that airway inflammation triggered by mucoid P. aeruginosa is less responsive to the anti-inflammatory action of corticosteroids. Whether this translates into a diminished response of CF patients to corticosteroid therapy should be examined in future clinical studies.

scholarly journals Pseudomonas Pyocyanin Increases Interleukin-8 Expression by Human Airway Epithelial Cells

1998 ◽  
Vol 66 (12) ◽  
pp. 5777-5784 ◽  
Author(s):  
Gerene M. Denning ◽  
Laura A. Wollenweber ◽  
Michelle A. Railsback ◽  
Charles D. Cox ◽  
Lynn L. Stoll ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Lung Disease ◽  
Protein Kinases ◽  
Tyrosine Kinases ◽  
Oxidant Stress ◽  
Airway Epithelial Cells ◽  
Interleukin 8 ◽  
Airway Epithelial ◽  
Necrosis Factor Alpha ◽  
Rnase Protection

ABSTRACT Pseudomonas aeruginosa, an opportunistic human pathogen, causes acute pneumonia in patients with hospital-acquired infections and is commonly associated with chronic lung disease in individuals with cystic fibrosis (CF). Evidence suggests that the pathophysiological effects of P. aeruginosa are mediated in part by virulence factors secreted by the bacterium. Among these factors is pyocyanin, a redox active compound that increases intracellular oxidant stress. We find that pyocyanin increases release of interleukin-8 (IL-8) by both normal and CF airway epithelial cell lines and by primary airway epithelial cells. Moreover, pyocyanin synergizes with the inflammatory cytokines tumor necrosis factor alpha and IL-1α. RNase protection assays indicate that increased IL-8 release is accompanied by increased levels of IL-8 mRNA. The antioxidant n -acetyl cysteine, general inhibitors of protein tyrosine kinases, and specific inhibitors of mitogen-activated protein kinases diminish pyocyanin-dependent increases in IL-8 release. Conversely, inhibitors of protein kinases C (PKC) and PKA have no effect. In contrast to its effects on IL-8 expression, pyocyanin inhibits cytokine-dependent expression of the monocyte/macrophage/T-cell chemokine RANTES. Increased release of IL-8, a potent neutrophil chemoattractant, in response to pyocyanin could contribute to the marked infiltration of neutrophils and subsequent neutrophil-mediated tissue damage that are observed inPseudomonas-associated lung disease.

Differentiation of human pluripotent stem cells into airway epithelial cells

Pneumologie ◽  
2015 ◽  
Vol 69 (07) ◽  
Author(s):  
S Ulrich ◽  
S Weinreich ◽  
R Haller ◽  
S Menke ◽  
R Olmer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial Cells ◽  
Pluripotent Stem Cells ◽  
Airway Epithelial Cells ◽  
Human Pluripotent Stem Cells ◽  
Airway Epithelial

Differential regulation of the transcriptomic and secretomic landscape of sensor and effector funtions of human airway epithelial cells

Pneumologie ◽  
2018 ◽  
Vol 72 (S 01) ◽  
pp. S100-S101
Author(s):  
R Lehmann ◽  
M Müller ◽  
TE Klassert ◽  
D Driesch ◽  
M Stock ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Differential Regulation ◽  
Airway Epithelial ◽  
Human Airway ◽  
Human Airway Epithelial Cells
Sign in / Sign up

Export Citation Format

Share Document