scholarly journals Tobacco Smoke and Inhaled Drugs Alter Expression and Activity of Multidrug Resistance-Associated Protein-1 (MRP1) in Human Distal Lung Epithelial Cells in vitro

2020 ◽  
Vol 8 ◽  
Author(s):  
Mohammed Ali Selo ◽  
Anne-Sophie Delmas ◽  
Lisa Springer ◽  
Viktoria Zoufal ◽  
Johannes A. Sake ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Epithelial Cells ◽  
Tobacco Smoke ◽  
Lung Epithelial Cells ◽  
Inhaled Drugs ◽  
Lung Epithelial ◽  
Distal Lung ◽  
Expression And Activity

scholarly journals Expression and Activity of Breast Cancer Resistance Protein (BCRP/ABCG2) in Human Distal Lung Epithelial Cells In Vitro

2017 ◽  
Vol 34 (12) ◽  
pp. 2477-2487 ◽  
Author(s):  
Sabrina Nickel ◽  
Mohammed Ali Selo ◽  
Juliane Fallack ◽  
Caoimhe G. Clerkin ◽  
Hanno Huwer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Breast Cancer Resistance Protein ◽  
Lung Epithelial Cells ◽  
Cancer Resistance ◽  
Lung Epithelial ◽  
Resistance Protein ◽  
Distal Lung ◽  
Expression And Activity

scholarly journals Effect of Slit/Robo signaling on regeneration in lung emphysema

2021 ◽  
Author(s):  
Jin-Soo Park ◽  
RyeonJin Cho ◽  
Eun-Young Kang ◽  
Yeon-Mok Oh
Keyword(s):  
Epithelial Cells ◽  
Mouse Model ◽  
Lung Epithelial Cells ◽  
Mouse Lung ◽  
Chronic Obstructive ◽  
Irreversible Damage ◽  
Lung Epithelial ◽  
And Migration ◽  
Proliferation And Migration

AbstractEmphysema, a pathological component of chronic obstructive pulmonary disease, causes irreversible damage to the lung. Previous studies have shown that Slit plays essential roles in cell proliferation, angiogenesis, and organ development. In this study, we evaluated the effect of Slit2 on the proliferation and migration of mouse lung epithelial cells and its role in regeneration in an emphysema lung mouse model. Here, we have shown that Slit2/Robo signaling contributes to the regeneration of lungs damaged by emphysema. Mouse epithelial lung cells treated with Slit2 exhibited increased proliferation and migration in vitro. Our results also showed that Slit2 administration improved alveolar regeneration in the emphysema mouse model in vivo. Furthermore, Slit2/Robo signaling increased the phosphorylation of ERK and Akt, which was mediated by Ras activity. These Slit2-mediated cellular signaling processes may be involved in the proliferation and migration of mouse lung epithelial cells and are also associated with the potential mechanism of lung regeneration. Our findings suggest that Slit2 administration may be beneficial for alveolar regeneration in lungs damaged by emphysema.

scholarly journals SARS-CoV-2 Infection-Induced Promoter Hypomethylation as an Epigenetic Modulator of Heat Shock Protein A1L (HSPA1L) Gene

2021 ◽  
Vol 12 ◽  
Author(s):  
Jibran Sualeh Muhammad ◽  
Narjes Saheb Sharif-Askari ◽  
Zheng-Guo Cui ◽  
Mawieh Hamad ◽  
Rabih Halwani
Keyword(s):  
Epithelial Cells ◽  
Mrna Expression ◽  
Candidate Genes ◽  
Epigenetic Regulation ◽  
Dna Methyltransferases ◽  
Lung Epithelial Cells ◽  
Potential Candidate ◽  
Blood Samples ◽  
Lung Epithelial

Numerous researches have focused on the genetic variations affecting SARS-CoV-2 infection, whereas the epigenetic effects are inadequately described. In this report, for the first time, we have identified potential candidate genes that might be regulated via SARS-CoV-2 induced DNA methylation changes in COVID-19 infection. At first, in silico transcriptomic data of COVID-19 lung autopsies were used to identify the top differentially expressed genes containing CpG Islands in their promoter region. Similar gene regulations were also observed in an in vitro model of SARS-CoV-2 infected lung epithelial cells (NHBE and A549). SARS-CoV-2 infection significantly decreased the levels of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) in lung epithelial cells. Out of 14 candidate genes identified, the expression of 12 genes was upregulated suggesting promoter hypomethylation, while only two genes were downregulated suggesting promoter hypermethylation in COVID-19. Among those 12 upregulated genes, only HSPA1L and ULBP2 were found to be upregulated in AZA-treated lung epithelial cells and immune cells, suggesting their epigenetic regulation. To confirm the hypomethylation of these two genes during SARS-CoV-2 infection, their promoter methylation and mRNA expression levels were determined in the genomic DNA/RNA obtained from whole blood samples of asymptomatic, severe COVID-19 patients and equally matched healthy controls. The methylation level of HSPA1L was significantly decreased and the mRNA expression was increased in both asymptomatic and severe COVID-19 blood samples suggesting its epigenetic regulation by SARS-CoV-2 infection. Functionally, HSPA1L is known to facilitate host viral replication and has been proposed as a potential target for antiviral prophylaxis and treatment.

Inhibition of amiloride-sensitive sodium-channel activity in distal lung epithelial cells by nitric oxide

1998 ◽  
Vol 274 (3) ◽  
pp. L378-L387 ◽  
Author(s):  
Jin Wen Ding ◽  
John Dickie ◽  
Hugh O’Brodovich ◽  
Yutaka Shintani ◽  
Bijan Rafii ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Epithelial Cells ◽  
Cell Function ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Lung Epithelial Cells ◽  
Flufenamic Acid ◽  
Activated Macrophages ◽  
Lung Epithelial ◽  
Distal Lung

Distal lung epithelial cells (DLECs) play an active role in fluid clearance from the alveolus by virtue of their ability to actively transport Na+ from the alveolus to the interstitial space. The present study evaluated the ability of activated macrophages to modulate the bioelectric properties of DLECs. Low numbers of lipopolysaccharide (LPS)-treated macrophages were able to significantly reduce amiloride-sensitive short-circuit current ( I sc) without affecting total I sc or monolayer resistance. This was associated with a rise in the flufenamic acid-sensitive component of the I sc. The effect was reversed by the addition of N-monomethyl-l-arginine to the medium, implying a role for nitric oxide. We hypothesized that macrophages exerted their effect by expressing inducible nitric oxide synthase (iNOS) in DLECs. The products of LPS-treated macrophages increased the levels of iNOS protein and mRNA transcripts in DLECs as well as causing a rise in iNOS activity. Immunofluorescence microscopy of LPS-stimulated macrophage-DLEC cocultures with anti-nitrotyrosine antibodies provided evidence for the generation of peroxynitrite in macrophages but not in DLECs. These data indicate that activated macrophages in the lung may contribute to impaired resolution of acute respiratory distress syndrome and suggest a novel mechanism whereby nitric oxide might alter cell function by altering its ion-transporting phenotype.

scholarly journals SARS-CoV-2 Spike 1 Protein Controls Natural Killer Cell Activation via the HLA-E/NKG2A Pathway

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1975 ◽  
Author(s):  
Daria Bortolotti ◽  
Valentina Gentili ◽  
Sabrina Rizzo ◽  
Antonella Rotola ◽  
Roberta Rizzo
Keyword(s):  
Epithelial Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Cell Activation ◽  
Nk Cell ◽  
Killer Cell ◽  
Lung Epithelial Cells ◽  
Lung Epithelial ◽  
Spike Proteins

Natural killer cells are important in the control of viral infections. However, the role of NK cells during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has previously not been identified. Peripheral blood NK cells from SARS-CoV and SARS-CoV-2 naïve subjects were evaluated for their activation, degranulation, and interferon-gamma expression in the presence of SARS-CoV and SARS-CoV-2 spike proteins. K562 and lung epithelial cells were transfected with spike proteins and co-cultured with NK cells. The analysis was performed by flow cytometry and immune fluorescence. SARS-CoV and SARS-CoV-2 spike proteins did not alter NK cell activation in a K562 in vitro model. On the contrary, SARS-CoV-2 spike 1 protein (SP1) intracellular expression by lung epithelial cells resulted in NK cell-reduced degranulation. Further experiments revealed a concomitant induction of HLA-E expression on the surface of lung epithelial cells and the recognition of an SP1-derived HLA-E-binding peptide. Simultaneously, there was increased modulation of the inhibitory receptor NKG2A/CD94 on NK cells when SP1 was expressed in lung epithelial cells. We ruled out the GATA3 transcription factor as being responsible for HLA-E increased levels and HLA-E/NKG2A interaction as implicated in NK cell exhaustion. We show for the first time that NK cells are affected by SP1 expression in lung epithelial cells via HLA-E/NKG2A interaction. The resulting NK cells’ exhaustion might contribute to immunopathogenesis in SARS-CoV-2 infection.

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