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American Journal of Physiology. Lung Cellular and Molecular Physiology

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https://www.readbyqxmd.com/read/29770701/mk2-mediates-macrophage-activation-and-acute-lung-injury-by-regulating-let-7e-mirna
#1
Yaxian Wu, Huiqiong He, Yunhe Ding, Sirui Liu, Depeng Zhang, Jun Wang, Hongchao Jiang, Dan Zhang, Lei Sun, Richard D Ye, Feng Qian
MAPK-activated protein kinase 2 (MK2) plays a critical role in the development of inflammation. However, the modulatory mechanisms in macrophage activation and acute lung injury (ALI) haven't been completely defined. Here, we reported that MK2 deficient mice (MK2-/-) protected against sepsis-induced ALI. In response to lipopolysaccharide (LPS) challenge, MK2-/- mice and myeloid cell-specific MK2 conditional knockout mice (MK2Lyz2-KO) exhibited attenuated inflammatory response, especially producing fewer amounts of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and macrophage inflammatory protein 2 (MIP-2)...
May 17, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29745255/pannexin-1-channels-on-endothelial-cells-mediate-vascular-inflammation-during-lung-ischemia-reperfusion-injury
#2
Ashish K Sharma, Eric J Charles, Yunge Zhao, Adishesh K Narahari, Pranav K Baderdinni, Miranda E Good, Ulrike M Lorenz, Irving L Kron, Douglas A Bayliss, Kodi S Ravichandran, Brant E Isakson, Victor E Laubach
Ischemia-reperfusion injury (IRI), which involves inflammation, vascular permeability, and edema, remains a major challenge after lung transplantation. Pannexin 1 (Panx1) channels modulate cellular ATP release during inflammation. This study tests the hypothesis that endothelial Panx1 is a key mediator of vascular inflammation and edema after IR and that IRI can be blocked by Panx1 antagonism. A murine hilar ligation model of IRI was utilized whereby left lungs underwent 1 hour of ischemia and 2 hours of reperfusion...
May 10, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29745254/treatment-of-rat-congenital-diaphragmatic-hernia-with-sildenafil-and-ns-304-selexipag-s-active-compound-at-the-pseudoglandular-stage-improves-lung-vasculature
#3
Daphne S Mous, Heleen M Kool, Petra E Burgisser, Marjon J Buscop-van Kempen, Koji Nagata, Anne Boerema-de Munck, Joost van Rosmalen, Oleh Dzyubachyk, Rene Mh Wijnen, Dick Tibboel, Robbert J Rottier
Patients with congenital diaphragmatic hernia (CDH) often suffer from severe pulmonary hypertension and the choice of current vasodilator therapy is mostly based on trial and error. Since pulmonary vascular abnormalities are already present early during development, we performed a study to modulate these pulmonary vascular changes at an early stage during gestation. Pregnant Sprague-Dawley rats were treated with nitrofen at day 9.5 of gestation (E9.5) to induce CDH in the offspring and subsequently the phosphodiesterase-5 inhibitor sildenafil and/or the novel prostaglandin-I receptor agonist selexipag (NS-304) were administered from E17...
May 10, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29745253/pulmonary-artery-smooth-muscle-cell-hif-1%C3%AE-regulates-endothelin-expression-via-microrna-543
#4
Ching-Chia Wang, Lihua Ying, Elizabeth A Barnes, Eloa S Adams, Francis Y Kim, Karl W Engel, Cristina M Alvira, David N Cornfield
Pulmonary artery smooth muscle cells (PASMC) express endothelin (ET-1) which modulates the pulmonary vascular response to hypoxia. Although cross-talk between hypoxia-inducible factor-1α (HIF-1α), an O2 -sensitive transcription factor, and ET-1 is established, the cell-specific relationship between HIF-1α and ET-1 expression remains incompletely understood. We tested the hypotheses that in PASMC: (i) HIF-1α expression constrains ET-1 expression; and (ii) a specific microRNA (miRNA) links HIF-1α and ET-1 expression...
May 10, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29745252/changes-in-the-pattern-of-fibrosis-in-the-rat-lung-with-repetitive-orotracheal-instillations-of-gastric-contents-evidence-of-persistent-collagen-accumulation
#5
Pedro Ayala, Jorge Torres, Raul Vivar, Pablo R Olmos, Manuel Meneses, Gisella R Borzone
Recurrent aspiration of gastric contents has been associated with several interstitial lung diseases. Despite this association, the pathogenic role of aspiration in these diseases has been poorly studied and little is known about extracellular matrix (ECM) changes in animal models of repetitive events of aspiration. Our aim was to study the repair phase of lung injury induced by each of several instillations of gastric fluid in Sprague-Dawley rats to evaluate changes in ECM and their reversibility. Anesthetized animals received weekly orotracheal instillations of gastric fluid for 1, 2, 3 and 4 weeks and were sacrificed at day 7 after last instillation...
May 10, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29745251/amd3100-ameliorates-cigarette-smoke-induced-emphysema-like-manifestations-in-mice
#6
Daria Barwinska, Houssam Oueini, Christophe Poirier, Marjorie E Albrecht, Natalia V Bogatcheva, Matthew J Justice, Jacob Saliba, Kelly S Schweitzer, Hal E Broxmeyer, Keith L March, Irina Petrache
We have shown that cigarette smoke (CS)-induced pulmonary emphysema-like manifestations are preceded by marked suppression of the number and function of bone marrow hematopoietic progenitor cells (HPC). To investigate if a limited availability of HPC may contribute to CS-induced lung injury, we used an FDA-approved antagonist of the interactions of SDF-1 with its receptor CXCR4 to promote intermittent HPC mobilization and tested its ability to limit emphysema-like injury following chronic CS. We administered AMD3100 (5mg/kg) to mice during a chronic CS exposure protocol of up to 24 weeks...
May 10, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29722567/alveolar-epithelial-cell-processing-of-nanoparticles-activates-autophagy-and-lysosomal-exocytosis
#7
Arnold Sipos, Kwang-Jin Kim, Robert H Chow, Per Flodby, Zea Borok, Edward D Crandall
Utilizing confocal microscopy, we quantitatively assessed uptake, processing and egress of near infrared (NIR)-labeled carboxylated polystyrene nanoparticles (PNP) in live alveolar epithelial cells (AEC) during interactions with primary rat AEC monolayers (RAECM). PNP fluorescence intensity (content) and colocalization with intracellular vesicles in a cell were determined over the entire cell volume via z-stacking. Isotropic cuvette-based microfluorimetry was used to determine PNP concentration ([PNP]) from anisotropic measurements of PNP content assessed by confocal microscopy...
May 3, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29722566/inhibition-of-raf1-ameliorates-bleomycin-induced-pulmonary-fibrosis-through-attenuation-of-tgf%C3%AE-1-signaling
#8
Shuang Li, Jia Liu, Jiangning Tan, Lian Li, Mary J Kaltreider, Jing Zhao, Daniel J Kass, Dong Shang, Yutong Zhao
Idiopathic Pulmonary Fibrosis (IPF) is a fatal fibrotic lung disease associated with aberrant activation and differentiation of fibroblasts, leading to abnormal extracellular matrix (ECM) production. Currently, it is still an untreatable disease except lung transplantation. Here, we demonstrate that the Raf1 inhibitor GW5074 ameliorates lung fibrosis in bleomycin-induced pulmonary fibrosis. Post-treatment with GW5074 reduced fibronectin (FN) expression, collagen deposition, and inflammatory cell infiltration in bleomycin-challenged mice, suggesting an anti-fibrotic property of GW5074...
May 3, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29722565/mmp-12-activates-protease-activated-receptor-par-1-upregulates-placenta-growth-factor-and-leads-to-pulmonary-emphysema
#9
Hsin-Han Hou, Hao-Chien Wang, Shih-Lung Cheng, Yen-Fu Chen, Kai-Zen Lu, Chong-Jen Yu
Due to the expansion of aging and smoking populations, chronic pulmonary obstructive disease (COPD) is predicted to be the third leading cause of death worldwide in 2030. It is therefore pertinent to develop effective therapy to improve management for COPD. Cigarette smoke-mediated protease-antiprotease imbalance is a major pathogenic mechanism for COPD and results in massive pulmonary infiltration of neutrophils and macrophages, releasing excessive neutrophil elastase (NE) and matrix metalloproteinases (MMPs)...
May 3, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29722564/long-term-culture-and-cloning-of-primary-human-bronchial-basal-cells-that-maintain-multipotent-differentiation-capacity-and-cftr-channel-function
#10
Jennifer Ruth Peters-Hall, Melissa L Coquelin, Michael J Torres, Ryan LaRanger, Busola Ruth Alabi, Sei Sho, Jose Francisco Calva-Moreno, Philip J Thomas, Jerry William Shay
While primary cystic fibrosis (CF) and non-CF human bronchial epithelial basal cells (HBECs) accurately represent in vivo phenotypes, one barrier to their wider use has been a limited ability to clone and expand cells in sufficient numbers to produce rare genotypes using genome editing tools. Recently, conditional reprogramming of cells (CRC) with a ROCK inhibitor and culture on an irradiated fibroblast feeder layer resulted in extension of the lifespan of HBECs, but differentiation capacity and CF transmembrane conductance regulator (CFTR) function decreased as a function of passage...
May 3, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29722563/damage-associated-molecular-patterns-damps-in-resuscitated-hemorrhagic-shock-are-mitigated-by-peritoneal-fluid-administration
#11
Paul J Matheson, Mark A Eid, Matthew A Wilson, Victoria S Graham, Samuel A Matheson, Jessica Lee Weaver, Cynthia D Downard, Jason W Smith
INTRODUCTION: Conventional resuscitation (CR) of hemorrhagic shock (HS), a significant cause of trauma mortality, is I.V. blood and fluids. CR restores central hemodynamics, but vital organ flow can drop causing hypoperfusion, hypoxia, Damage-Associated Molecular Patterns (DAMPs), and remote organ dysfunction (i.e., lung). CR plus Direct Peritoneal Resuscitation (DPR) prevents intestinal and hepatic hypoperfusion. We hypothesized that DPR prevents lung injury in HS/CR by altering DAMPs...
May 3, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29722562/nmda-receptor-activation-inhibits-the-anti-fibrotic-effect-of-bm-mscs-on-bleomycin-induced-pulmonary-fibrosis
#12
Xiao-Hong Li, Chen Li, Yiting Tang, Yan-Hong Huang, Qing-Mei Cheng, Xiao-Ting Huang, Feiyan Zhao, Cai-Xia Hao, Dan-Dan Feng, Jian-Ping Xu, Jianzhong Han, Siyuan Tang, Wei Liu, Shaojie Yue, Zi-Qiang Luo
Endogenous glutamate (Glu) release and N-methyl-D-aspartate (NMDA) receptor (NMDAR) activation are associated with lung injury in different animal models. However, the underlying mechanism is unclear. Bone marrow-derived mesenchymal stem cells (BM-MSCs), which show potential use for immunomodulation and tissue-protection, play a protective role in pulmonary fibrosis (PF) process. Here, we found the increased Glu release from the BM cells of bleomycin (BLM)-induced PF mice in vivo. BLM stimulation also increased the extracellular Glu in BM-MSCs via the antiporter system xc- in vitro...
May 3, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29722561/the-role-of-non-coding-rnas-in-regulating-epithelial-responses-in-copd
#13
Yifan Chen, Paul S Thomas, Rakesh K Kumar, Cristan Herbert
Chronic obstructive pulmonary disease (COPD), one of the leading causes of death in the world, is a chronic inflammatory disease of the airways usually caused by long-term exposure to inhaled irritants. Airway epithelial cells (AECs) play a key role in initializing COPD and driving the exacerbation of this disease through the release of various cytokines. This AEC-derived cytokine response is tightly regulated possibly through the regulatory effects of non-coding RNAs (ncRNAs). Although the importance of ncRNAs in pulmonary diseases has been increasingly realized, little is known about the role of ncRNA in the regulation of inflammatory responses in COPD...
May 3, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29722560/intrauterine-growth-restriction-decreases-nuclear-factor-kappa-b-signaling-in-fetal-pulmonary-artery-endothelial-cells-of-fetal-sheep
#14
R Blair Dodson, Kyle N Powers, Jason Gien, Paul J Rozance, Gregory J Seedorf, David Astling, Kenneth Lloyd Jones, Timothy M Crombleholme, Steven H Abman, Cristina M Alvira
Intrauterine growth restriction (IUGR) in premature newborns increases the risk for bronchopulmonary dysplasia (BPD), a chronic lung disease characterized by disrupted pulmonary angiogenesis and alveolarization. We previously showed that experimental IUGR impairs angiogenesis, however, mechanisms that impair pulmonary artery endothelial cell (PAEC) function are uncertain. The nuclear factor-kappa-B (NFκB) pathway promotes vascular growth in the developing mouse lung, and we hypothesized that IUGR disrupts NFκB-regulated pro-angiogenic targets in fetal PAEC...
May 3, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29722559/mir-142-3p-is-associated-with-aberrant-wingless-integrase-i-wnt-signaling-during-airway-remodeling-in-asthma
#15
Sabine Bartel, Gianni Carraro, Francesca Alessandrini, Susanne Krauss-Etschmann, Fabio L M Ricciardolo, Saverio Bellusci
BACKGROUND: Asthma is characterized by a chronic inflammation and remodeling of the airways. While inflammation can be controlled, therapeutic options to revert remodeling do not exist. Thus, there is a large and unmet need to understand the underlying molecular mechanisms in order to develop novel therapies. OBJECTIVE: we previously identified a pivotal role for miR-142-3p in regulating airway smooth muscle precursor (ASM) cell proliferation during lung development by fine-tuning the Wingless/Integrase I (WNT) signaling...
May 3, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29722558/is-fibroblast-growth-factor-signaling-pathway-a-victim-of-receptor-tyrosine-kinase-inhibition-in-pulmonary-parenchymal-and-vascular-remodeling
#16
Elie El Agha, Felix Schwind, Clemens Ruppert, Andreas Günther, Saverio Bellusci, Ralph Theo Schermuly, Djuro Kosanovic
Idiopathic pulmonary arterial hypertension (IPAH), pulmonary hypertension (PH) due to lung disease and/or hypoxia and idiopathic pulmonary fibrosis (IPF) are increasingly recognized as important contributors to mortality and morbidity worldwide. Among others, the current treatment paradigm considers broad inhibition of receptor tyrosine kinases, a strategy that likely leads to collateral inhibition of signaling pathways that are critical for lung repair and regeneration. Fibroblast growth factor 7 (FGF7) and FGF10 signaling in the lung through FGF receptor 2 (FGFR2) are involved in epithelial cell protection and renewal, and mutations in their corresponding genes in humans are linked to increased susceptibility to lung pathologies such as chronic obstructive pulmonary disease and bronchopulmonary dysplasia...
May 3, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29696987/fabp4-regulates-eosinophil-recruitment-and-activation-in-allergic-airway-inflammation
#17
Xiao Na Ge, Idil Bastan, Mythili Dileepan, Yana Greenberg, Sung Gil Ha, Kaylee A Steen, David A Bernlohr, Savita P Rao, P Sriramarao
Fatty acid binding protein 4 (FABP4), a member of a family of lipid-binding proteins, is known to play a role in inflammation by virtue of its ability to regulate intracellular events such as lipid fluxes and signaling. Studies have indicated a pro-inflammatory role for FABP4 in allergic asthma, although its expression and function in eosinophils, the predominant inflammatory cells recruited to allergic airways, was not investigated. We examined expression of FABP4 in murine eosinophils and its role in regulating cell recruitment in vitro as well as in cockroach antigen (CRA)-induced allergic airway inflammation...
April 26, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29696986/fibroblast-senescence-in-the-pathology-of-idiopathic-pulmonary-fibrosis
#18
David W Waters, Kaj E C Blokland, Prabuddha S Pathinayake, Janette K Burgess, Steven E Mutsaers, Cecilia M Prêle, Michael Schuliga, Christopher L Grainge, Darryl A Knight
Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia of unknown cause with a median survival of only 3 years. Little is known about the mechanisms that precede the excessive collagen deposition seen in IPF, but cellular senescence has been strongly implicated in disease pathology. Senescence is a state of irreversible cell cycle arrest accompanied by an abnormal secretory profile and is thought to play a critical role in both development and wound repair. Normally, once a senescent cell has contributed to wound repair it is promptly removed from the environment via infiltrating immune cells...
April 26, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29671605/effects-of-budesonide-and-surfactant-in-preterm-fetal-sheep
#19
T Brett Kothe, Emily Royse, Matthew W Kemp, Augusto F Schmidt, Fabrizio Salomone, Masatoshi Saito, Haruo Usuda, Shimpei Watanabe, Gabrielle C Musk, Alan H Jobe, Noah H Hillman
BACKGROUND: Mechanical ventilation causes lung injury and systemic inflammatory responses in preterm sheep, and is associated with bronchopulmonary dysplasia (BPD) in preterm infants. Budesonide added to surfactant decreased BPD by 20% in infants. OBJECTIVE: Determine the effects of budesonide and surfactant on injury from high tidal volume (VT) ventilation in preterm lambs. METHODS: Ewes at 125 {plus minus} 1 day GA had fetal surgery to expose fetal head and chest with placental circulation intact...
April 19, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29671604/neuropilin-2-regulates-airway-inflammatory-responses-to-inhaled-lipopolysaccharide
#20
Robert M Immormino, David C Lauzier, Hideki Nakano, Michelle L Hernandez, Neil E Alexis, Andrew L Ghio, Stephen L Tilley, Claire M Doerschuk, David B Peden, Donald N Cook, Timothy P Moran
Neuropilins are multifunctional receptors that play important roles in immune regulation. Neuropilin-2 (NRP2) is expressed in the lungs, but whether it regulates airway immune responses is unknown. Here, we report that Nrp2 is weakly expressed by alveolar macrophages (AM) in the steady-state, but is dramatically up-regulated following in vivo lipopolysaccharide (LPS) inhalation. Ex vivo treatment of human AM with LPS also increased NRP2 mRNA expression and cell-surface display of NRP2 protein. LPS-induced Nrp2 expression in AM was dependent upon the MyD88 signaling pathway and the transcription factor nuclear factor kappa B (NFκB)...
April 19, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
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