scholarly journals Regulation of IL-33 by Oncostatin M in Mouse Lung Epithelial Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Carl D. Richards ◽  
Laura Izakelian ◽  
Anisha Dubey ◽  
Grace Zhang ◽  
Steven Wong ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Alveolar Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Oncostatin M ◽  
Mouse Lung ◽  
Nuclear Staining ◽  
Potent Inducer ◽  
Alveolar Epithelial ◽  
Lung Epithelial

IL-33 modulates both innate and adaptive immune responses at tissue sites including lung and may play critical roles in inflammatory lung disease. Although IL-33 expression can be altered upon NF-Kappa B activation, here we examine regulation by Oncostatin M, a gp130 cytokine family member, in mouse lung tissue. Responses were assessed in BALB/c mouse lung at day 7 of transient overexpression using endotracheally administered adenovirus encoding OSM (AdOSM) or empty vector (AdDel70). Whole lung extracts showed induction of IL-33 mRNA (>20-fold) and protein (10-fold increase in immunoblots) by AdOSM relative to AdDel70. Immunohistochemistry for IL-33 indicated a marked induction of nuclear staining in alveolar epithelial cellsin vivo. Oncostatin M stimulated IL-33 mRNA and IL-33 full length protein in C10 mouse type 2 alveolar epithelial cells in culture in time-dependent and dose-dependent fashion, whereas IL-6, LIF, IL-31, IL-4, or IL-13 did not, and TGFβrepressed IL-33. IL-33 induction was associated with activation of STAT3, and pharmacological inhibition of STAT3 ameliorated IL-33 levels. These results indicate Oncostatin M as a potent inducer of IL-33 in mouse lung epithelial cells and suggest that an OSM/IL-33 axis may participate in innate immunity and inflammatory conditions in lung.

scholarly journals Role of Acinetobactin-Mediated Iron Acquisition Functions in the Interaction of Acinetobacter baumannii Strain ATCC 19606Twith Human Lung Epithelial Cells, Galleria mellonella Caterpillars, and Mice

2012 ◽  
Vol 80 (3) ◽  
pp. 1015-1024 ◽  
Author(s):  
Jennifer A. Gaddy ◽  
Brock A. Arivett ◽  
Michael J. McConnell ◽  
Rafael López-Rojas ◽  
Jerónimo Pachón ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Acinetobacter Baumannii ◽  
Galleria Mellonella ◽  
Ex Vivo ◽  
Iron Acquisition ◽  
Alveolar Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Content Type ◽  
Alveolar Epithelial

Acinetobacter baumannii, which causes serious infections in immunocompromised patients, expresses high-affinity iron acquisition functions needed for growth under iron-limiting laboratory conditions. In this study, we determined that the initial interaction of the ATCC 19606Ttype strain with A549 human alveolar epithelial cells is independent of the production of BasD and BauA, proteins needed for acinetobactin biosynthesis and transport, respectively. In contrast, these proteins are required for this strain to persist within epithelial cells and cause their apoptotic death. Infection assays usingGalleria mellonellalarvae showed that impairment of acinetobactin biosynthesis and transport functions significantly reduces the ability of ATCC 19606Tcells to persist and kill this host, a defect that was corrected by adding inorganic iron to the inocula. The results obtained with theseex vivoandin vivoapproaches were validated using a mouse sepsis model, which showed that expression of the acinetobactin-mediated iron acquisition system is critical for ATCC 19606Tto establish an infection and kill this vertebrate host. These observations demonstrate that the virulence of the ATCC 19606Tstrain depends on the expression of a fully active acinetobactin-mediated system. Interestingly, the three models also showed that impairment of BasD production results in an intermediate virulence phenotype compared to those of the parental strain and the BauA mutant. This observation suggests that acinetobactin intermediates or precursors play a virulence role, although their contribution to iron acquisition is less relevant than that of mature acinetobactin.

Expression and functional implications of CCR2 expression on murine alveolar epithelial cells

2004 ◽  
Vol 286 (1) ◽  
pp. L68-L72 ◽  
Author(s):  
Paul J. Christensen ◽  
Ming Du ◽  
Bethany Moore ◽  
Susan Morris ◽  
Galen B. Toews ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Lung Injury ◽  
Basement Membranes ◽  
Alveolar Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Alveolar Epithelial ◽  
Ccr2 Expression ◽  
Lung Epithelial ◽  
Functional Consequences ◽  
Delayed Closure

Acute lung injury results in damage to the alveolar epithelium, leading to leak of proteins into the alveolar space and impaired gas exchange. Lung function can be restored only if the epithelial layer is restored. The process of reepithelialization requires migration of lung epithelial cells to cover denuded basement membranes. The factors that control the migration of lung epithelial cells are incompletely understood. We examined isolated murine type II alveolar epithelial cells (AECs) for expression of CC chemokine receptor 2 (CCR2) and functional consequences of the binding of the main CCR2 ligand monocyte chemoattractant protein-1 (MCP-1). We found that primary AECs bound MCP-1 and expressed CCR2 mRNA. These cells demonstrated functional consequences of CCR2 expression with migration in response to MCP-1 in chemotaxis/haptotaxis assays. Primary AECs cultured from mice lacking CCR2 did not respond to MCP-1. Monolayers of AECs lacking CCR2 demonstrated delayed closure of mechanical wounds compared with AEC monolayers expressing CCR2. Delayed closure of mechanical wounds of wild-type AECs was also demonstrated in the presence of anti-MCP-1 antibody. These data demonstrate for the first time that AECs express CCR2 and are capable of using this receptor for chemotaxis and healing of wounds. CCR2-MCP-1 interactions may be important in the process of reepithelialization after lung injury.

Mechanical stretching of alveolar epithelial cells increases Na+-K+-ATPase activity

1999 ◽  
Vol 87 (2) ◽  
pp. 715-721 ◽  
Author(s):  
Christopher M. Waters ◽  
Karen M. Ridge ◽  
G. Sunio ◽  
K. Venetsanou ◽  
Jacob Iasha Sznajder
Keyword(s):  
Epithelial Cells ◽  
Atpase Activity ◽  
Basolateral Membrane ◽  
Alveolar Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Cyclic Stretch ◽  
Lung Edema ◽  
Alveolar Epithelial ◽  
A Cell

Alveolar epithelial cells effect edema clearance by transporting Na+ and liquid out of the air spaces. Active Na+ transport by the basolaterally located Na+-K+-ATPase is an important contributor to lung edema clearance. Because alveoli undergo cyclic stretch in vivo, we investigated the role of cyclic stretch in the regulation of Na+-K+-ATPase activity in alveolar epithelial cells. Using the Flexercell Strain Unit, we exposed a cell line of murine lung epithelial cells (MLE-12) to cyclic stretch (30 cycles/min). After 15 min of stretch (10% mean strain), there was no change in Na+-K+-ATPase activity, as assessed by86Rb+uptake. By 30 min and after 60 min, Na+-K+-ATPase activity was significantly increased. When cells were treated with amiloride to block amiloride-sensitive Na+ entry into cells or when cells were treated with gadolinium to block stretch-activated, nonselective cation channels, there was no stimulation of Na+-K+-ATPase activity by cyclic stretch. Conversely, cells exposed to Nystatin, which increases Na+ entry into cells, demonstrated increased Na+-K+-ATPase activity. The changes in Na+-K+-ATPase activity were paralleled by increased Na+-K+-ATPase protein in the basolateral membrane of MLE-12 cells. Thus, in MLE-12 cells, short-term cyclic stretch stimulates Na+-K+-ATPase activity, most likely by increasing intracellular Na+ and by recruitment of Na+-K+-ATPase subunits from intracellular pools to the basolateral membrane.

scholarly journals Time-resolved dual RNA-Seq reveals extensive rewiring of lung epithelial and pneumococcal transcriptomes during early infection

2016 ◽  
Author(s):  
Rieza Aprianto ◽  
Jelle Slager ◽  
Siger Holsappel ◽  
Jan-Willem Veening
Keyword(s):  
Epithelial Cells ◽  
Pneumococcal Infection ◽  
Alveolar Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Infection Model ◽  
Rna Seq ◽  
Time Resolved ◽  
Alveolar Epithelial ◽  
Lung Epithelial ◽  
Host Microbe Interactions

AbstractStreptococcus pneumoniae(pneumococcus) is the main etiological agent of pneumonia. Pneumococcal pneumonia is initiated by bacterial adherence to lung epithelial cells. Infection to the epithelium is a disruptive interspecies interaction involving numerous transcription-mediated processes. Revealing transcriptional changes may provide valuable insights into pneumococcal disease. Dual RNA-Seq allows simultaneous monitoring of the transcriptomes of both host and pathogen. Here, we developed a time-resolved infection model of human lung alveolar epithelial cells byS. pneumoniaeand assessed transcriptome changes by dual RNA-Seq. Our data provide new insights into host-microbe interactions and show that the epithelial glutathione-detoxification pathway is activated by bacterial presence. We observed that adherent pneumococci, not free-floating bacteria, access host-associated carbohydrates and repress innate immune responses. In conclusion, we provide a dynamic dual-transcriptomics overview of early pneumococcal infection with easy online access (http://dualrnaseq.molgenrug.nl). Further database exploration may expand our understanding of epithelial-pneumococcal interaction, leading to novel antimicrobial strategies.Graphical Abstract

scholarly journals Francisella tularensis Invasion of Lung Epithelial Cells

2008 ◽  
Vol 76 (7) ◽  
pp. 2833-2842 ◽  
Author(s):  
Robin R. Craven ◽  
Joshua D. Hall ◽  
James R. Fuller ◽  
Sharon Taft-Benz ◽  
Thomas H. Kawula
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Francisella Tularensis ◽  
Bacterial Pathogen ◽  
Alveolar Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Mouse Lung ◽  
Epithelial Cell Line ◽  
Bacterial Surface ◽  
Lung Epithelial

ABSTRACT Francisella tularensis, a gram-negative facultative intracellular bacterial pathogen, causes disseminating infections in humans and other mammalian hosts. Macrophages and other monocytes have long been considered the primary site of F. tularensis replication in infected animals. However, recently it was reported that F. tularensis also invades and replicates within alveolar epithelial cells following inhalation in a mouse model of tularemia. TC-1 cells, a mouse lung epithelial cell line, were used to study the process of F. tularensis invasion and intracellular trafficking within nonphagocytic cells. Live and paraformaldehyde-fixed F. tularensis live vaccine strain organisms associated with, and were internalized by, TC-1 cells at similar frequencies and with indistinguishable differences in kinetics. Inhibitors of microfilament and microtubule activity resulted in significantly decreased F. tularensis invasion, as did inhibitors of phosphatidylinositol 3-kinase and tyrosine kinase activity. Collectively, these results suggest that F. tularensis epithelial cell invasion is mediated by a preformed ligand on the bacterial surface and driven entirely by host cell processes. Once internalized, F. tularensis-containing endosomes associated with early endosome antigen 1 (EEA1) followed by lysosome-associated membrane protein 1 (LAMP-1), with peak coassociation frequencies occurring at 30 and 120 min postinoculation, respectively. By 2 h postinoculation, 70.0% (± 5.5%) of intracellular bacteria were accessible to antibody delivered to the cytoplasm, indicating vacuolar breakdown and escape into the cytoplasm.

Resveratrol inhibits Staphylococcus aureus-induced TLR2/MyD88/NF-κB-dependent VCAM-1 expression in human lung epithelial cells

2014 ◽  
Vol 127 (6) ◽  
pp. 375-390 ◽  
Author(s):  
I-Ta Lee ◽  
Chih-Chung Lin ◽  
Chih-Kai Hsu ◽  
Ming-Yen Wu ◽  
Rou-Ling Cho ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Epithelial Cells ◽  
Human Lung ◽  
Alveolar Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Polyphenolic Compound ◽  
Alveolar Epithelial ◽  
Lung Epithelial ◽  
Dependent Pathway ◽  
Human Lung Epithelial Cells

In the present study, we found that S. aureus induced VCAM-1 expression in human pulmonary alveolar epithelial cells via a TLR2/MyD88/NF-κB-dependent pathway, which was inhibited by treatment with the polyphenolic compound resveratrol.

scholarly journals TRIM72 modulates caveolar endocytosis in repair of lung cells

2016 ◽  
Vol 310 (5) ◽  
pp. L452-L464 ◽  
Author(s):  
Nagaraja Nagre ◽  
Shaohua Wang ◽  
Thomas Kellett ◽  
Ragu Kanagasabai ◽  
Jing Deng ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Cell Injury ◽  
Alveolar Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Functional Domain ◽  
Physical Interaction ◽  
Type I ◽  
Alveolar Epithelial ◽  
Lung Epithelial

Alveolar epithelial and endothelial cell injury is a major feature of the acute respiratory distress syndrome, in particular when in conjunction with ventilation therapies. Previously we showed [Kim SC, Kellett T, Wang S, Nishi M, Nagre N, Zhou B, Flodby P, Shilo K, Ghadiali SN, Takeshima H, Hubmayr RD, Zhao X. Am J Physiol Lung Cell Mol Physiol 307: L449–L459, 2014.] that tripartite motif protein 72 (TRIM72) is essential for amending alveolar epithelial cell injury. Here, we posit that TRIM72 improves cellular integrity through its interaction with caveolin 1 (Cav1). Our data show that, in primary type I alveolar epithelial cells, lack of TRIM72 led to significant reduction of Cav1 at the plasma membrane, accompanied by marked attenuation of caveolar endocytosis. Meanwhile, lentivirus-mediated overexpression of TRIM72 selectively increases caveolar endocytosis in rat lung epithelial cells, suggesting a functional association between these two. Further coimmunoprecipitation assays show that deletion of either functional domain of TRIM72, i.e., RING, B-box, coiled-coil, or PRY-SPRY, abolishes the physical interaction between TRIM72 and Cav1, suggesting that all theoretical domains of TRIM72 are required to forge a strong interaction between these two molecules. Moreover, in vivo studies showed that injurious ventilation-induced lung cell death was significantly increased in knockout (KO) TRIM72KO and Cav1KO lungs compared with wild-type controls and was particularly pronounced in double KO mutants. Apoptosis was accompanied by accentuation of gross lung injury manifestations in the TRIM72KO and Cav1KO mice. Our data show that TRIM72 directly and indirectly modulates caveolar endocytosis, an essential process involved in repair of lung epithelial cells through removal of plasma membrane wounds. Given TRIM72's role in endomembrane trafficking and cell repair, we consider this molecule an attractive therapeutic target for patients with injured lungs.

Bleomycin initiates apoptosis of lung epithelial cells by ROS but not by Fas/FasL pathway

2006 ◽  
Vol 290 (4) ◽  
pp. L790-L796 ◽  
Author(s):  
Shulamit B. Wallach-Dayan ◽  
Gabriel Izbicki ◽  
Pazit Y. Cohen ◽  
Regina Gerstl-Golan ◽  
Alan Fine ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Mouse Lung ◽  
Caspase 8 ◽  
Caspase 9 ◽  
Lung Epithelial ◽  
Induced Apoptosis

Epithelial cells are considered to be a main target of bleomycin-induced lung injury, which leads to fibrosis in vivo. We studied the characteristics of in vitro bleomycin-induced apoptosis in a mouse lung epithelial (MLE) cell line. Bleomycin caused an increase of reactive oxygen species (ROS) resulting in oxidative stress, mitochondrial leakage, and apoptosis. These were associated with elevated caspase-8 and resultant caspase-9 activity and with upregulation of Fas expression. Glutathione and inhibitors of caspase-8 or caspase-9, but not of FasL, inhibited these effects, suggesting their dependence on ROS, caspase-8 and -9, in a Fas/FasL-independent pathway. However, postbleomycin-exposed MLE cells were more sensitive to Fas-mediated apoptosis. These results demonstrate that the initial bleomycin-induced oxidative stress causes a direct apoptotic effect in lung epithelial cells involving a regulatory role of caspase-8 on caspase-9. Fas represents an amplification mechanism, and not a direct trigger of bleomycin-induced epithelial cell apoptosis.

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