scholarly journals Influenza virus infection alters ion channel function of airway and alveolar cells: mechanisms and physiological sequelae

2017 ◽  
Vol 313 (5) ◽  
pp. L845-L858 ◽  
Author(s):  
James David Londino ◽  
Ahmed Lazrak ◽  
James F. Collawn ◽  
Zsuzsanna Bebok ◽  
Kevin S. Harrod ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Bacterial Infections ◽  
Alveolar Epithelial Cell ◽  
Ionic Composition ◽  
Influenza Virus Infection ◽  
Alveolar Epithelial Cells ◽  
Alveolar Cells ◽  
Alveolar Epithelial

The cystic fibrosis transmembrane conductance regulator (CFTR) and the amiloride-sensitive epithelial sodium channels (ENaC) are located in the apical membranes of airway and alveolar epithelial cells. These transporters play an important role in the regulation of lung fluid balance across airway and alveolar epithelia by being the conduits for chloride (Cl−) and bicarbonate ([Formula: see text]) secretion and sodium (Na+) ion absorption, respectively. The functional role of these channels in the respiratory tract is to maintain the optimum volume and ionic composition of the bronchial periciliary fluid (PCL) and alveolar lining fluid (ALF) layers. The PCL is required for proper mucociliary clearance of pathogens and debris, and the ALF is necessary for surfactant homeostasis and optimum gas exchange. Dysregulation of ion transport may lead to mucus accumulation, bacterial infections, inflammation, pulmonary edema, and compromised respiratory function. Influenza (or flu) in mammals is caused by influenza A and B viruses. Symptoms include dry cough, sore throat, and is often followed by secondary bacterial infections, accumulation of fluid in the alveolar spaces and acute lung injury. The underlying mechanisms of flu symptoms are not fully understood. This review summarizes our present knowledge of how influenza virus infections alter airway and alveolar epithelial cell CFTR and ENaC function in vivo and in vitro and the role of these changes in influenza pathogenesis.

scholarly journals Polymerase Acidic Subunit of H9N2 Polymerase Complex Induces Cell Apoptosis by Binding to PDCD 7 in A549 Cells

2020 ◽  
Author(s):  
Shaohua Wang ◽  
Na Li ◽  
Shugang Jin ◽  
Ruihua Zhang ◽  
Tong Xu
Keyword(s):  
Cell Death ◽  
Influenza Virus ◽  
Cell Apoptosis ◽  
Influenza A ◽  
A549 Cells ◽  
Influenza Virus Infection ◽  
Economic Loss ◽  
Poultry Production ◽  
H9n2 Influenza Virus

Abstract Background: H9N2 influenza virus, a subtype of influenza A virus, can spread across different species and induce the respiratory infectious disease in humans, leading to a severe public health risk and a huge economic loss to poultry production. Increasing studies have shown that polymerase acidic (PA) subunit of RNA polymerase in ribonucleoproteins complex of H9N2 involves in crossing the host species barriers, the replication and airborne transmission of H9N2.Methods: Here, to further investigate the role of PA subunit during the infection of H9N2 influenza virus, we employed mass spectrometry (MS) to search the potential binding proteins of PA subunit of H9N2. Our MS results showed that programmed cell death protein 7 (PDCD7) is a binding target of PA subunit. Co-immunoprecipitation and pull-down assays further confirmed the interaction between PDCD7 and PA subunit. Overexpression of PA subunit in A549 lung cells greatly increased the levels of PDCD7 in the nuclear and induced cell death assayed by MTT assay.Results: Flow cytometry analysis and Western blot results showed that PA subunit overexpression significantly increased the expression of pro-apoptotic protein, bax and caspase 3, and induced cell apoptosis. However, knockout of PDCD7 effectively attenuated the effects of PA overexpression in cell apoptosis.Conclusions: In conclusion, the PA subunit of H9N2 bind with PDCD7 and regulated cell apoptosis, which provide new insights in the role of PA subunit during H9N2 influenza virus infection.

Progranulin aggravates pulmonary immunopathology during influenza virus infection

Thorax ◽  
2018 ◽  
Vol 74 (3) ◽  
pp. 305-308 ◽  
Author(s):  
Qin Luo ◽  
Xingxing Yan ◽  
Hongmei Tu ◽  
Yibing Yin ◽  
Ju Cao
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Inflammatory Diseases ◽  
Influenza Virus Infection ◽  
Epithelial Barrier ◽  
Alveolar Epithelial ◽  
Cytokines And Chemokines ◽  
Deficient Mice ◽  
Experimental Influenza

Progranulin (PGRN) exerts multiple functions in various inflammatory diseases. However, the role of PGRN in the pathogenesis of virus infection is unknown. Here, we demonstrated that PGRN production was up-regulated in clinical and experimental influenza, which contributed to the deleterious inflammatory response after influenza virus infection in mice. PGRN-deficient mice were protected from influenza virus-induced lung injury and mortality. Decreased mortality was associated with significantly reduced influx of neutrophils and monocytes/macrophages, release of cytokines and chemokines, and permeability of the alveolar–epithelial barrier without affecting viral clearance. Our findings suggest that PGRN exacerbates pulmonary immunopathology during influenza virus infection.

scholarly journals Differential Susceptibilities of Human Lung Primary Cells to H1N1 Influenza Viruses

2015 ◽  
Vol 89 (23) ◽  
pp. 11935-11944 ◽  
Author(s):  
Emily Travanty ◽  
Bin Zhou ◽  
Hongbo Zhang ◽  
Y. Peter Di ◽  
John F. Alcorn ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Human Lung ◽  
Influenza Virus Infection ◽  
Alveolar Epithelial Cells ◽  
Host Susceptibility ◽  
Epithelial Barrier ◽  
Primary Cells ◽  
Alveolar Epithelial ◽  
Increased Susceptibility ◽  
Human Alveolar Epithelial Cells

ABSTRACTHuman alveolar epithelial cells (AECs) and alveolar macrophages (AMs) are the first lines of lung defense. Here, we report that AECs are the direct targets for H1N1 viruses that have circulated since the 2009 pandemic (H1N1pdm09). AMs are less susceptible to H1N1pdm09 virus, but they produce significantly more inflammatory cytokines than AECs from the same donor. AECs form an intact epithelial barrier that is destroyed by H1N1pdm09 infection. However, there is significant variation in the cellular permissiveness to H1N1pdm09 infection among different donors. AECs from obese donors appear to be more susceptible to H1N1pdm09 infection, whereas gender, smoking history, and age do not appear to affect AEC susceptibility. There is also a difference in response to different strains of H1N1pdm09 viruses. Compared to A/California04/09 (CA04), A/New York/1682/09 (NY1682) is more infectious and causes more epithelial barrier injury, although it stimulates less cytokine production. We further determined that a single amino acid residue substitution in NY1682 hemagglutinin is responsible for the difference in infectivity. In conclusion, this is the first study of host susceptibility of human lung primary cells and the integrity of the alveolar epithelial barrier to influenza. Further elucidation of the mechanism of increased susceptibility of AECs from obese subjects may facilitate the development of novel protection strategies against influenza virus infection.IMPORTANCEDisease susceptibility of influenza is determined by host and viral factors. Human alveolar epithelial cells (AECs) form the key line of lung defenses against pathogens. Using primary AECs from different donors, we provided cellular level evidence that obesity might be a risk factor for increased susceptibility to influenza. We also compared the infections of two closely related 2009 pandemic H1N1 strains in AECs from the same donor and identified a key viral factor that affected host susceptibility, the dominance of which may be correlated with disease epidemiology. In addition, primary human AECs can serve as a convenient and powerful model to investigate the mechanism of influenza-induced lung injury and determine the effect of genetic and epigenetic factors on host susceptibility to pandemic influenza virus infection.

LncRNA SAL-RNA1 Knockdown Suppressed Pink1-Mediated Mitophagy Protects Against CS-Induced Alveolar Cells Senescence Through Regulation of Sirt1

2021 ◽  
Author(s):  
Hui Jiang ◽  
Yaqing Li ◽  
Yuanri Xu ◽  
Yaona Jiang ◽  
Dong Yuan
Keyword(s):  
Underlying Mechanism ◽  
Alveolar Epithelial Cells ◽  
Chronic Obstructive ◽  
Alveolar Cells ◽  
Obstructive Pulmonary Disease ◽  
Phosphatase And Tensin Homolog ◽  
Alveolar Epithelial ◽  
Tensin Homolog ◽  
Putative Protein Kinase

Abstract Background LncRNAs pays an important roles in the regulation of alveolar cells in cigarette smoke (CS) induced chronic obstructive pulmonary disease (COPD). However, the role of lncRNA SAL-RNA1 in promoting mitophagy and reduces senescence of alveolar cells in COPD is unknow. Methods This study is aims to elucidate the underlying mechanism of LncRNA SAL-RNA1 and phosphatase and tensin homolog (PTEN)-induced putative protein kinase 1 (PINK1) expression were upregulated in alveolar of emphysema mice and CS treated alveolar epithelial cells. LncRNA SAL-RNA1 knockdown suppressed mitophagy and induced senescence of alveolar cells while overexpressing lncRNA SAL-RNA1 promoted mitophagy and reduced the senescence of alveolar cells. In addition, lncRNA SAL-RNA1 interacted with Sirt1 and regulated the upgradation of Sirt1. Results We further found lncRNA SAL-RNA1 regulated Pink1 expression through Sirt1. Mechanistically, lncRNA SAL-RNA1 regulated PinK1-mediated mitophagy and senescence of alveolar cells through regulation Sirt1. Conclusion Finally, overexpression lncRNA SAL-RNA1 promote mitophagy and relieved emphysema.

scholarly journals Human Staufen1 Protein Interacts with Influenza Virus Ribonucleoproteins and Is Required for Efficient Virus Multiplication

2010 ◽  
Vol 84 (15) ◽  
pp. 7603-7612 ◽  
Author(s):  
Susana de Lucas ◽  
Joan Peredo ◽  
Rosa María Marión ◽  
Carmen Sánchez ◽  
Juan Ortín
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A ◽  
Particle Production ◽  
Nonstructural Protein ◽  
A549 Cells ◽  
Influenza Virus Infection ◽  
Ns1 Protein ◽  
Infected Cells

ABSTRACT The influenza A virus genome consists of 8 negative-stranded RNA segments. NS1 is a nonstructural protein that participates in different steps of the virus infectious cycle, including transcription, replication, and morphogenesis, and acts as a virulence factor. Human Staufen1 (hStau1), a protein involved in the transport and regulated translation of cellular mRNAs, was previously identified as a NS1-interacting factor. To investigate the possible role of hStau1 in the influenza virus infection, we characterized the composition of hStau1-containing granules isolated from virus-infected cells. Viral NS1 protein and ribonucleoproteins (RNPs) were identified in these complexes by Western blotting, and viral mRNAs and viral RNAs (vRNAs) were detected by reverse transcription (RT)-PCR. Also, colocalization of hStau1 with NS1, nucleoprotein (NP), and PA in the cytosol of virus-infected cells was shown by immunofluorescence. To analyze the role of hStau1 in the infection, we downregulated its expression by gene silencing. Human HEK293T cells or A549 cells were silenced using either short hairpin RNAs (shRNAs) or small interfering RNAs (siRNAs) targeting four independent sites in the hStau1 mRNA. The yield of influenza virus was reduced 5 to 10 times in the various hStau1-silenced cells compared to that in control silenced cells. The expression levels of viral proteins and their nucleocytoplasmic localization were not affected upon hStau1 silencing, but virus particle production, as determined by purification of virions from supernatants, was reduced. These results indicate a role for hStau1 in late events of the influenza virus infection, possibly during virus morphogenesis.

scholarly journals Alveolar Epithelial Cells Direct Monocyte Transepithelial Migration upon Influenza Virus Infection: Impact of Chemokines and Adhesion Molecules

2006 ◽  
Vol 177 (3) ◽  
pp. 1817-1824 ◽  
Author(s):  
Susanne Herold ◽  
Werner von Wulffen ◽  
Mirko Steinmueller ◽  
Stephan Pleschka ◽  
William A. Kuziel ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Epithelial Cells ◽  
Virus Infection ◽  
Adhesion Molecules ◽  
Influenza Virus Infection ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial

A cGAS-dependent response links DNA damage and senescence in alveolar epithelial cells: A potential drug target in IPF

2021 ◽  
Author(s):  
Michael Schuliga ◽  
Amama Kanwal ◽  
Jane Read ◽  
Kaj Erik Cornelis Blokland ◽  
Janette K. Burgess ◽  
...  
Keyword(s):  
Dna Damage ◽  
Epithelial Cell ◽  
Alveolar Epithelial Cell ◽  
Primary Cultures ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Sirna Knockdown ◽  
Interfering Rna ◽  
Culture Supernatants

Alveolar epithelial cell (AEC) senescence is implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Mitochondrial dysfunction including release of mitochondrial DNA (mtDNA) is a feature of senescence, which led us to investigate the role of the DNA-sensing GMP-AMP synthase (cGAS) in IPF, with a focus on AEC senescence. cGAS expression in fibrotic tissue from lungs of IPF patients was detected within cells immunoreactive for epithelial cell adhesion molecule (EpCAM) and p21, epithelial and senescence markers respectively. Submerged primary cultures of AECs isolated from lung tissue of IPF patients (IPF-AECs, n=5) exhibited higher baseline senescence than AECs from control donors (Ctrl-AECs, n=5-7), as assessed by increased nuclear histone 2AXγ phosphorylation, p21 mRNA and expression of senescence-associated secretory phenotype (SASP) cytokines. Pharmacological cGAS inhibition using RU.521 diminished IPF-AEC senescence in culture and attenuated induction of Ctrl-AEC senescence following etoposide-induced DNA damage. Short interfering RNA (siRNA) knockdown of cGAS also attenuated etoposide-induced senescence of the AEC line, A549. Higher levels of mtDNA were detected in the cytosol and culture supernatants of primary IPF- and etoposide-treated Ctrl-AECs when compared to Ctrl-AECs at baseline. Furthermore, ectopic mtDNA augmented cGAS-dependent senescence of Ctrl-AECs, whereas DNAse I treatment diminished IPF-AEC senescence. This study provides evidence that a self-DNA driven, cGAS-dependent response augments AEC senescence, identifying cGAS as a potential therapeutic target for IPF.

Chloride and potassium channel function in alveolar epithelial cells

2003 ◽  
Vol 284 (5) ◽  
pp. L689-L700 ◽  
Author(s):  
Scott M. O'Grady ◽  
So Yeong Lee
Keyword(s):  
Epithelial Cells ◽  
Fluid Layer ◽  
Ionic Composition ◽  
Basolateral Membrane ◽  
Alveolar Epithelium ◽  
Alveolar Epithelial Cells ◽  
Apical Surface ◽  
Alveolar Cell ◽  
Alveolar Epithelial

Electrolyte transport across the adult alveolar epithelium plays an important role in maintaining a thin fluid layer along the apical surface of the alveolus that facilitates gas exchange across the epithelium. Most of the work published on the transport properties of alveolar epithelial cells has focused on the mechanisms and regulation of Na+ transport and, in particular, the role of amiloride-sensitive Na+ channels in the apical membrane and the Na+-K+-ATPase located in the basolateral membrane. Less is known about the identity and role of Cl− and K+ channels in alveolar epithelial cells, but studies are revealing important functions for these channels in regulation of alveolar fluid volume and ionic composition. The purpose of this review is to examine previous work published on Cl− and K+ channels in alveolar epithelial cells and to discuss the conclusions and speculations regarding their role in alveolar cell transport function.

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