AJP: Lung Cellular and Molecular Physiology This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Nedd8 modification of Cullin-5 regulates lipopolysaccharide-induced acute lung injury
In this study, we investigated the potential role of Cul-5 in regulating ALI using mice receiving intratracheal instillation of LPS. We observed that Cul-5-deficient mice displayed reduced lung injury compared with wild-type mice as evidenced by histological analysis, alveolar neutrophil infiltration, and lung liquid accumulation. In addition, inflammatory cytokine expression in bronchoalveolar lavage fluid and lung tissue was also markedly reduced in LPS-treated Cul-5-deficient mice. Interestingly, intratracheal adoptive transfer of Cul-5+/– but not Cul-5+/+ macrophages attenuated neutrophil recruitment, alveolar in...
Source: AJP: Lung Cellular and Molecular Physiology - July 1, 2017 Category: Respiratory Medicine Authors: Zhu, Z., Sun, L., Hao, R., Jiang, H., Qian, F., Ye, R. D. Tags: RESEARCH ARTICLE Source Type: research

Modified mesenchymal stem cells using miRNA transduction alter lung injury in a bleomycin model
Although different preclinical models have demonstrated a favorable role for bone marrow-derived mesenchymal stem cells (B-MSC) in preventing fibrosis, this protective effect is not observed with late administration of these cells, when fibrotic changes are consolidated. We sought to investigate whether the late administration of B-MSCs overexpressing microRNAs (miRNAs) let-7d (antifibrotic) or miR-154 (profibrotic) could alter lung fibrosis in a murine bleomycin model. Using lentiviral vectors, we transduced miRNAs (let-7d or miR-154) or a control sequence into human B-MSCs. Overexpression of let-7d or miR-154 was associa...
Source: AJP: Lung Cellular and Molecular Physiology - July 1, 2017 Category: Respiratory Medicine Authors: Huleihel, L., Sellares, J., Cardenes, N., Alvarez, D., Faner, R., Sakamoto, K., Yu, G., Kapetanaki, M. G., Kaminski, N., Rojas, M. Tags: RESEARCH ARTICLE Source Type: research

Low-dose cadmium exposure induces peribronchiolar fibrosis through site-specific phosphorylation of vimentin
Exposure to cadmium (Cd) has been associated with development of chronic obstructive lung disease (COPD). The mechanisms and signaling pathways whereby Cd causes pathological peribronchiolar fibrosis, airway remodeling, and subsequent airflow obstruction remain unclear. We aimed to evaluate whether low-dose Cd exposure induces vimentin phosphorylation and Yes-associated protein 1 (YAP1) activation leading to peribronchiolar fibrosis and subsequent airway remodeling. Our data demonstrate that Cd induces myofibroblast differentiation and extracellular matrix (ECM) deposition around small (<2 mm in diameter) airways. Upon ...
Source: AJP: Lung Cellular and Molecular Physiology - July 1, 2017 Category: Respiratory Medicine Authors: Li, F. J., Surolia, R., Li, H., Wang, Z., Liu, G., Liu, R.-M., Mirov, S. B., Athar, M., Thannickal, V. J., Antony, V. B. Tags: RESEARCH ARTICLE Source Type: research

The effects of electronic cigarette aerosol exposure on inflammation and lung function in mice
This study aimed to assess whether exposure to electronic cigarette (e-cigarette) aerosol would alter lung function and pulmonary inflammation in mice and to compare the severity of any alterations with mice exposed to mainstream tobacco smoke. Female BALB/c mice were exposed for 8 wk to tobacco smoke, medical air (control), or one of four different types of e-cigarette aerosol. E-cigarette aerosols varied depending on nicotine content (0 or 12 mg/ml) and the main excipient (propylene glycol or glycerin). Twenty-four hours after the final exposure, we measured pulmonary inflammation, lung volume, lung mechanics, and respon...
Source: AJP: Lung Cellular and Molecular Physiology - July 1, 2017 Category: Respiratory Medicine Authors: Larcombe, A. N., Janka, M. A., Mullins, B. J., Berry, L. J., Bredin, A., Franklin, P. J. Tags: RESEARCH ARTICLE Source Type: research

Flavored e-cigarette liquids reduce proliferation and viability in the CALU3 airway epithelial cell line
E-cigarettes are generally thought of as a safer smoking alternative to traditional cigarettes. However, little is known about the effects of e-cigarette liquids (e-liquids) on the lung. Since over 7,000 unique flavors have been identified for purchase in the United States, our goal was to conduct a screen that would test whether different flavored e-liquids exhibited different toxicant profiles. We tested the effects of 13 different flavored e-liquids [with nicotine and propylene glycol/vegetable glycerin (PG/VG) serving as controls] on a lung epithelial cell line (CALU3). Using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphen...
Source: AJP: Lung Cellular and Molecular Physiology - July 1, 2017 Category: Respiratory Medicine Authors: Rowell, T. R., Reeber, S. L., Lee, S. L., Harris, R. A., Nethery, R. C., Herring, A. H., Glish, G. L., Tarran, R. Tags: RESEARCH ARTICLE Source Type: research

CD44high alveolar type II cells show stem cell properties during steady-state alveolar homeostasis
The alveolar epithelium is composed of type I cells covering most of the gas-blood exchange surface and type II cells secreting surfactant that lowers surface tension of alveoli to prevent alveolar collapse. Here, we have identified a subgroup of type II cells expressing a higher level of cell surface molecule CD44 (CD44high type II cells) that composed ~3% of total type II cells in 5–10-wk-old mice. These cells were preferentially apposed to lung capillaries. They displayed a higher proliferation rate and augmented differentiation capacity into type I cells and the ability to form alveolar organoids compared with CD...
Source: AJP: Lung Cellular and Molecular Physiology - July 1, 2017 Category: Respiratory Medicine Authors: Chen, Q., Suresh Kumar, V., Finn, J., Jiang, D., Liang, J., Zhao, Y.-y., Liu, Y. Tags: RESEARCH ARTICLE Source Type: research

Autophagy plays a role in FSTL1-induced epithelial mesenchymal transition and airway remodeling in asthma
In this study, we hypothesized that Follistatin-like 1 (FSTL1) promotes EMT and airway remodeling by intensifying autophagy. With the use of transmission electron microscopy (TEM), double-membrane autophagosomes were detected in the airways of patients and mice. More autophagosomes were in patients with asthma and OVA-challenged mice compared with healthy controls. The expression of FSTL1 and beclin-1 was upregulated in the airways of patients with asthma and OVA-challenged mice, accompanied by airway EMT and remodeling. In OVA-challenged Fstl1+/– mice, the degree of airway remodeling and autophagy was decreased comp...
Source: AJP: Lung Cellular and Molecular Physiology - July 1, 2017 Category: Respiratory Medicine Authors: Liu, T., Liu, Y., Miller, M., Cao, L., Zhao, J., Wu, J., Wang, J., Liu, L., Li, S., Zou, M., Xu, J., Broide, D. H., Dong, L. Tags: RESEARCH ARTICLE Source Type: research

Klotho, an antiaging molecule, attenuates oxidant-induced alveolar epithelial cell mtDNA damage and apoptosis
Alveolar epithelial cell (AEC) apoptosis and inadequate repair resulting from "exaggerated" lung aging and mitochondrial dysfunction are critical determinants promoting lung fibrosis. α-Klotho, which is an antiaging molecule that is expressed predominantly in the kidney and secreted in the blood, can protect lung epithelial cells against hyperoxia-induced apoptosis. We reasoned that Klotho protects AEC exposed to oxidative stress in part by maintaining mitochondrial DNA (mtDNA) integrity and mitigating apoptosis. We find that Klotho levels are decreased in both serum and alveolar type II (AT2) cells from asbestos-exp...
Source: AJP: Lung Cellular and Molecular Physiology - July 1, 2017 Category: Respiratory Medicine Authors: Kim, S.-J., Cheresh, P., Eren, M., Jablonski, R. P., Yeldandi, A., Ridge, K. M., Budinger, G. R. S., Kim, D.-H., Wolf, M., Vaughan, D. E., Kamp, D. W. Tags: RESEARCH ARTICLE Source Type: research

Acute brain trauma, lung injury, and pneumonia: more than just altered mental status and decreased airway protection
Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Even when patients survive the initial insult, there is significant morbidity and mortality secondary to subsequent pulmonary edema, acute lung injury (ALI), and nosocomial pneumonia. Whereas the relationship between TBI and secondary pulmonary complications is recognized, little is known about the mechanistic interplay of the two phenomena. Changes in mental status secondary to acute brain injury certainly impair airway- and lung-protective mechanisms. However, clinical and translational evidence suggests that more specific neuronal and ce...
Source: AJP: Lung Cellular and Molecular Physiology - July 1, 2017 Category: Respiratory Medicine Authors: Hu, P. J., Pittet, J.-F., Kerby, J. D., Bosarge, P. L., Wagener, B. M. Tags: REVIEW Source Type: research

Free actin impairs macrophage bacterial defenses via scavenger receptor MARCO interaction with reversal by plasma gelsolin
Lung injury can release intracellular actin into the alveolar milieu and is also associated with increased susceptibility to secondary infections. We investigated the effect of free (extracellular) actin on lung macrophage host defense functions. Western blot analysis demonstrated free actin release into the lung lavage fluids of mouse models of ozone injury, influenza infection, and secondary pneumococcal pneumonia and in samples from patients following burn and inhalation injury. Using levels comparable with those observed in lung injury, we found that free actin markedly inhibited murine lung macrophage binding and upta...
Source: AJP: Lung Cellular and Molecular Physiology - June 5, 2017 Category: Respiratory Medicine Authors: Ordija, C. M., Chiou, T. T.-Y., Yang, Z., Deloid, G. M., de Oliveira Valdo, M., Wang, Z., Bedugnis, A., Noah, T. L., Jones, S., Koziel, H., Kobzik, L. Tags: RESEARCH ARTICLE Source Type: research

Pyk2 phosphorylation of VE-PTP downstream of STIM1-induced Ca2+ entry regulates disassembly of adherens junctions
Vascular endothelial protein tyrosine phosphatase (VE-PTP) stabilizes endothelial adherens junctions (AJs) through constitutive dephosphorylation of VE-cadherin. Here we investigated the role of stromal interaction molecule 1 (STIM1) activation of store-operated Ca2+ entry (SOCE) in regulating AJ assembly. We observed that SOCE induced by STIM1 activated Pyk2 in human lung microvascular endothelial cells (ECs) and induced tyrosine phosphorylation of VE-PTP at Y1981. Pyk2-induced tyrosine phosphorylation of VE-PTP promoted Src binding to VE-PTP, Src activation, and subsequent VE-cadherin phosphorylation and thereby increase...
Source: AJP: Lung Cellular and Molecular Physiology - June 5, 2017 Category: Respiratory Medicine Authors: Soni, D., Regmi, S. C., Wang, D.-M., DebRoy, A., Zhao, Y.-Y., Vogel, S. M., Malik, A. B., Tiruppathi, C. Tags: RESEARCH ARTICLE Source Type: research

TNF{alpha} enhances force generation in airway smooth muscle
Airway inflammation is a hallmark of asthma, triggering airway smooth muscle (ASM) hyperreactivity and airway remodeling. TNFα increases both agonist-induced cytosolic Ca2+ concentration ([Ca2+]cyt) and force in ASM. The effects of TNFα on ASM force may also be due to an increase in Ca2+ sensitivity, cytoskeletal remodeling, and/or changes in contractile protein content. We hypothesized that 24 h of exposure to TNFα increases ASM force by changing actin and myosin heavy chain (MyHC) content and/or polymerization. Porcine ASM strips were permeabilized with 10% Triton X-100, and force was measured in respon...
Source: AJP: Lung Cellular and Molecular Physiology - June 5, 2017 Category: Respiratory Medicine Authors: Dogan, M., Han, Y.-S., Delmotte, P., Sieck, G. C. Tags: RESEARCH ARTICLE Source Type: research

ROR{alpha}-dependent type 2 innate lymphoid cells are required and sufficient for mucous metaplasia in immature mice
Early-life wheezing-associated respiratory tract infection by rhinovirus (RV) is considered a risk factor for asthma development. We have shown that RV infection of 6-day-old BALB/c mice, but not mature mice, induces an asthmalike phenotype that is associated with an increase in the population of type 2 innate lymphoid cells (ILC2s) and dependent on IL-13 and IL-25. We hypothesize that ILC2s are required and sufficient for development of the asthmalike phenotype in immature mice. Mice were infected with RV1B on day 6 of life and treated with vehicle or a chemical inhibitor of retinoic acid receptor-related orphan receptor-...
Source: AJP: Lung Cellular and Molecular Physiology - June 5, 2017 Category: Respiratory Medicine Authors: Rajput, C., Cui, T., Han, M., Lei, J., Hinde, J. L., Wu, Q., Bentley, J. K., Hershenson, M. B. Tags: RESEARCH ARTICLE Source Type: research

Newly divided eosinophils limit ozone-induced airway hyperreactivity in nonsensitized guinea pigs
Ozone causes vagally mediated airway hyperreactivity and recruits inflammatory cells, including eosinophils, to lungs, where they mediate ozone-induced hyperreactivity 1 day after exposure but are paradoxically protective 3 days later. We aimed to test the role of newly divided eosinophils in ozone-induced airway hyperreactivity in sensitized and nonsensitized guinea pigs. Nonsensitized and sensitized guinea pigs were treated with 5-bromo-2-deoxyuridine (BrdU) to label newly divided cells and were exposed to air or ozone for 4 h. Later (1 or 3 days later), vagally induced bronchoconstriction was measured, and inflammatory ...
Source: AJP: Lung Cellular and Molecular Physiology - June 5, 2017 Category: Respiratory Medicine Authors: Wicher, S. A., Jacoby, D. B., Fryer, A. D. Tags: RESEARCH ARTICLE Source Type: research

Apoptotic cell death in rat lung following mustard gas inhalation
To investigate apoptosis as a mechanism of sulfur mustard (SM) inhalation injury in animals, we studied different caspases (caspase-8, -9, -3, and -6) in the lungs from a ventilated rat SM aerosol inhalation model. SM activated all four caspases in cells obtained from bronchoalveolar lavage fluid (BALF) as early as 6 h after exposure. Caspase-8, which is known to initiate the extrinsic Fas-mediated pathway of apoptosis, was increased fivefold between 6 and 24 h, decreasing to the unexposed-control level at 48 h. The initiator, caspase-9, in the intrinsic mitochondrial pathway of apoptosis as well as the executioner caspase...
Source: AJP: Lung Cellular and Molecular Physiology - June 5, 2017 Category: Respiratory Medicine Authors: Andres, D. K., Keyser, B. M., Melber, A. A., Benton, B. J., Hamilton, T. A., Kniffin, D. M., Martens, M. E., Ray, R. Tags: RESEARCH ARTICLE Source Type: research