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American Journal of Respiratory Cell and Molecular Biology

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https://www.readbyqxmd.com/read/28613919/hypercapnia-accelerates-adipogenesis-a-novel-role-of-high-co2-in-exacerbating-obesity
#1
Ryota Kikuchi, Takao Tsuji, Osamu Watanabe, Kazuhiro Yamaguchi, Kinya Furukawa, Hiroyuki Nakamura, Kazutetsu Aoshiba
Obesity is a major risk factor for the development of obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS), which manifest as intermittent hypercapnia and sustained plus intermittent hypercapnia, respectively. In this study, we investigated whether CO2 affects adipocyte differentiation (adipogenesis) and maturation (hypertrophy). Human visceral or subcutaneous preadipocytes were grown to confluence and then induced to differentiate to adipocytes under hypocapnia, normocapnia, and hypercapnia with or without hypoxia...
June 14, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28613916/human-cd8-t-cells-damage-non-infected-epithelial-cells-during-influenza-virus-infection-in-vitro
#2
Carolien E van de Sandt, Montserrat Bárcena, Abraham J Koster, Jennifer Kasper, Charles J Kirkpatrick, Dana P Scott, Rory D de Vries, Susanne Herold, Guus F Rimmelzwaan, Thijs Kuiken, Kirsty R Short
During severe influenza A virus (IAV) infections a large amount of damage to the pulmonary epithelium is the result of the anti-viral immune response. Specifically, whilst CD8+ T cells are important for killing IAV-infected cells, during a severe IAV infection they can damage uninfected epithelial cells. At present, the mechanisms by which this occurs are unclear. Here, we used a novel in vitro co-culture model of human NCl-H441 cells and CD8+ T cells in order to provide a new insight into how CD8+ T cells may affect uninfected epithelial cells during severe IAV infections...
June 14, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28598679/hypoxia-modulates-epithelial-permeability-via-regulation-of-vascular-endothelial-growth-factor-in-airway-epithelia
#3
Hyun-Ah Song, Yoo-Suk Kim, Hyung-Ju Cho, Soo In Kim, Min Jung Kang, Ji Hyun Kim, Hyun Jin Min, Ju-Wan Kang, Joo-Heon Yoon, Chang-Hoon Kim
Hypoxia resulting from occlusion of the sinus ostium is known to be one of the major pathogenic mechanisms of sinusitis. Hypoxia-inducible factor-1 (HIF-1) is a widely known transcriptional factor that induces the cellular response to hypoxic conditions and activates the transcription of several genes, such as erythropoietin and vascular endothelial growth factor (VEGF). We hypothesized that induced permeability caused by hypoxia is a major pathophysiologic mechanism of upper airway disease such as sinusitis...
June 9, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28598206/a-novel-in-vitro-human-granuloma-model-of-sarcoidosis-and-latent-tb-infection
#4
Elliott D Crouser, Peter White, Evelyn Guirado Caceres, Mark W Julian, Audrey C Papp, Landon W Locke, Wolfgang Sadee, Larry S Schlesinger
Many aspects of pathogenic granuloma formation are poorly understood requiring new relevant laboratory models that represent the complexity (genetics and diversity) of human disease. To address this need, we developed an in vitro model of granuloma formation using human peripheral blood mononuclear cells (PBMCs) derived from patients with active sarcoidosis, latent tuberculosis (TB) infection (LTBI), or normal healthy controls. PBMCs were incubated for 7 days with uncoated polystyrene beads or beads coated with purified protein derivative (PPD) or human serum albumin (HSA)...
June 9, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28594573/activation-of-integrated-stress-response-and-metabolic-dysfunction-in-a-murine-model-of-sleep-apnea
#5
Abdelnaby Khalyfa, Zhuanhong Qiao, Alex Gileles-Hillel, Ahamed A Khalyfa, Mahzad Akbarpour, Brian Popko, David Gozal
BACKGROUND: Intermittent hypoxia (IH) induces activation of the integrated stress response (ISR), but its role in IH-induced visceral white adipose tissue (vWAT) insulin resistance in unknown. CHOP is activated by chronic ISR, while GADD34 dephosphorylates the subunit of translation initiation factor 2 (eIF2α), leading to termination of ISR. We hypothesized that CHOP/Gadd34 null mice would not manifest evidence of insulin resistance following IH exposures. METHODS: 8-week-old CHOP/GADD34-/- (DM) and wild type (WT) littermates were randomly assigned to IH or RA exposures for 6 weeks...
June 8, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28590142/intra-amniotic-soluble-endoglin-impairs-lung-development-in-neonatal-rats
#6
Santhosh T Somashekar, Ibrahim Sammour, Jian Huang, Juan Dominguez-Bendala, Ricardo Pastori, Silvia Alvarez-Cubela, Eneida Torres, Shu Wu, Karen C Young
Soluble endoglin (sENG) is increased in the amniotic fluid of mothers with pre-eclampsia and chorioamnionitis. Preterm infants born to mothers with these disorders have an increased risk of aberrant lung development. Whether this increased risk is secondary to elevated sENG levels is unclear. The objective of this study was to determine whether intrauterine exposure to an adenovirus over-expressing sENG impairs neonatal lung angiogenesis by modulating lung eNOS signaling. Pregnant Sprague-Dawley rats were randomly assigned to receive ultrasound guided intra-amniotic injections of adenovirus over-expressing sENG (Ad-sENG) or control adenovirus (Ad-control) on embryonic day 17 (E17)...
June 7, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28586276/dendritic-cell-trafficking-and-function-in-rare-lung-diseases
#7
Huan Liu, Claudia Jakubzick, Andrew R Osterburg, Rebecca L Nelson, Nishant Gupta, Francis X McCormack, Michael T Borchers
Dendritic cells (DCs) are highly specialized immune cells that capture antigens and then migrate to lymphoid tissue and present antigen to T cells. This critical function of DCs is well defined and recent studies further demonstrate that DCs are also key regulators of several innate immune responses. Studies focused on the roles of DCs in the pathogenesis of common lung diseases such as asthma, infection and cancer have traditionally driven our mechanistic understanding of pulmonary DC biology. The emerging development of novel DC reagents, techniques and genetically modified animal models has provided abundant data revealing distinct populations of DCs in the lung and allow us to examine mechanisms of DC development, migration and function in pulmonary disease with unprecedented detail...
June 6, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28586241/unbiased-quantitation-of-atii-to-ati-cell-transdifferentiation-during-repair-after-lung-injury-in-mice
#8
Nicole L Jansing, Jazalle McClendon, Peter M Henson, Rubin M Tuder, Dallas M Hyde, Rachel L Zemans
The alveolar epithelium consists of squamous alveolar type (AT)I and cuboidal ATII cells. ATI cells cover 95-98% of the alveolar surface, thereby playing a critical role in barrier integrity, and are extremely thin, thus permitting efficient gas exchange. During lung injury, ATI cells die, resulting in increased epithelial permeability. ATII cells reepithelialize the alveolar surface via proliferation and transdifferentiation into ATI cells. Transdifferentiation is characterized by downregulation of ATII cell markers, upregulation of ATI cell markers, and cell spreading resulting in a change in morphology from cuboidal to squamous, thus restoring normal alveolar architecture and function...
June 6, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28574721/a-multi-omics-approach-to-identify-genes-associated-with-childhood-asthma-risk-and-morbidity
#9
Erick Forno, Ting Wang, Qi Yan, John Brehm, Edna Acosta-Perez, Angel Colon-Semidey, Maria Alvarez, Nadia Boutaoui, Michelle M Cloutier, John F Alcorn, Glorisa Canino, Wei Chen, Juan C Celedón
RATIONALE: Childhood asthma is a complex disease. In this study, we aim to identify genes associated with childhood asthma through a multi-omics "vertical" approach that integrates multiple analytical steps using linear and logistic regression models. METHODS: In a case-control study of childhood asthma in Puerto Ricans (n=1127), we use adjusted linear or logistic regression models to evaluate associations between several analytical steps of omics data, including genome-wide (GW) genotype data, GW methylation, GW expression profiling, cytokine levels, asthma-intermediate phenotypes, and asthma status...
June 2, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28535074/synchrotron-imaging-shows-effect-of-ventilator-settings-on-intra-breath-cyclic-changes-in-pulmonary-blood-volume
#10
Liisa Porra, Ludovic Broche, Loïc Dégrugilliers, Gergely Albu, Iliona Malaspinas, Camille Doras, Mats Wallin, Magnus Hallbäck, Walid Habre, Sam Bayat
RATIONALE: Despite the importance of dynamic changes in the regional distributions of gas and blood during the breathing cycle for lung function in the mechanically ventilated patient, no quantitative data on such cyclic changes is currently available. METHODS: We used a novel gated synchrotron CT-imaging to quantitatively image regional lung gas (Vg), tissue density and blood volume (Vb) in 6 anaesthetized, paralyzed and mechanically ventilated rabbits with normal lungs...
May 23, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28530121/glucocorticoids-retain-bi-potent-fibroblast-progenitors-during-alveolar-septation-in-mice
#11
Stephen E McGowan, Diann M McCoy
Glucocorticoids have been widely used and exert pleiotropic effects on alveolar structure and function, but do not improve the long-term clinical outcomes for patients with bronchopulmonary dysplasia, emphysema, or interstitial lung diseases. Treatments which foster alveolar regeneration could substantially improve the long-term outcomes for such patients. One approach to alveolar regeneration is to stimulate and guide intrinsic alveolar progenitors along developmental pathways used during secondary septation...
May 21, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28489455/micrornas-profiling-in-asthma-potential-biomarkers-and-therapeutic-targets
#12
Enrico Heffler, Alessandro Allegra, Giovanni Pioggia, Giuseppe Picardi, Caterina Musolino, Sebastiano Gangemi
Asthma is a heterogeneous chronic inflammatory disease in which different endotypes contribute to define clinical-inflammatory phenotypes. MicroRNAs (miRNAs) are a class of small, endogenous 22-25 nt RNA molecules that bind to specific mRNAs to inhibit translation and promote mRNA degradation. miRNAs function in post-transcriptional regulation and control physiological and pathological processes in various diseases. The purpose of this review is to summarize and discuss the current knowledge on the function of miRNAs in asthma, focusing the attention particularly on their biological properties, pathophysiologic roles, and potential use as biomarkers and/or therapies for asthma...
May 10, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28489415/hepatic-steatosis-accompanies-pulmonary-alveolar-proteinosis
#13
Alan N Hunt, Anagha Malur, Tual Monfort, Pavlos Lagoudakis, Sumeet Mahajan, Anthony D Postle, Mary Jane Thomassen
Maintenance of tissue-specific organ lipid compositions characterises mammalian lipid homeostasis. Lung and liver synthesise mixed phosphatidylcholine (PC) molecular species subsequently "tailored" for function. Lungs progressively enrich disaturated PC (DSPC) directed to lamellar body (LB) surfactant stores prior to secretion. Liver accumulates polyunsaturated PC directed to VLDL assembly and secretion, or triglyceride stores. In each tissue, selective PC species enrichment mechanisms lie at the heart of effective homeostasis...
May 10, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28481637/hydrogen-sulfide-a-novel-player-in-airway-development-pathophysiology-of-respiratory-diseases-and-antiviral-defenses
#14
Nikolay Bazhanov, Maria Ansar, Teodora Ivanciuc, Roberto P Garofalo, Antonella Casola
Hydrogen sulfide (H2S) is a biologically relevant signaling molecule in mammals. Together with the volatile substances nitric oxide (NO) and carbon monoxide (CO), H2S is defined as a gasotransmitter, playing a physiological role in a variety of functions such as synaptic transmission, vascular tone, angiogenesis, inflammation and cellular signaling. The generation of H2S is catalyzed by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3 mercaptopyruvate sulfurtransferase (3-MST). The expression of CBS and CSE is tissue-specific with CBS being expressed predominantly in the brain and CSE in peripheral tissues, including lungs...
May 8, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28481622/cardiomyocytes-of-the-heart-and-pulmonary-veins-novel-contributors-to-asthma
#15
Stephen Sai Folmsbee, Cara J Gottardi
Recent genome-wide association studies have implicated both cardiac and pulmonary vein-related genes in the pathogenesis of asthma. Since cardiac cells are not present in lung airways or viewed to affect the immune system, interpretation of these findings in the context of more well-established contributors to asthma has remained challenging. However, cardiomyocytes are present in the lung, specifically along pulmonary veins, and recent murine models suggest that cardiac cells lining pulmonary veins may contribute to allergic airway disease...
May 8, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28481620/ifn%C3%AE-influences-epithelial-anti-viral-responses-via-histone-methylation-of-the-rig-i-promoter
#16
C Mirella Spalluto, Akul Singhania, Doriana Cellura, Christopher H Woelk, Tilman Sanchez-Elsner, Karl J Staples, Tom M A Wilkinson
The asthmatic lung is prone to respiratory viral infections that exacerbate the symptoms of the underlying disease. Recent work has suggested that a deficient Th1 response in early life may lead to these aberrant anti-viral responses. We investigated whether the inflammatory environment of the airway epithelium could modulate anti-viral gene expression via epigenetic mechanisms, in order to study the development of a long-term dysregulation of innate responses, which are a hallmark of asthma. We primed AALEB, a human bronchial epithelial cell line, with IFNγ and IL13 and subsequently infected cells with Respiratory Syncytial Virus (RSV) and innate anti-viral genes expression and their epigenetic markers were analysed...
May 8, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28463086/vitamin-d-counteracts-an-il-23-dependent-il-17a-ifn%C3%AE-response-driven-by-urban-particulate-matter
#17
Elizabeth H Mann, Tzer-Ren Ho, Paul E Pfeffer, Nick C Matthews, Elfy Chevretton, Ian Mudway, Frank J Kelly, Catherine M Hawrylowicz
Urban particulate matter (UPM) air pollution and vitamin D deficiency are detrimentally associated with respiratory health; this is hypothesised to be due in part to regulation of IL-17A, which UPM is reported to promote. Here we use a myeloid (m)DC-memory CD4+ T cell co-culture system to characterize UPM-driven IL-17A+ cells, investigate the mechanism by which UPM-primed DCs promote this phenotype and address evidence for cross-regulation by vitamin D. CD1c+ mDCs were cultured overnight with or without a reference source of UPM and/or active vitamin D (1,25(OH)2D3) before co-culturing with autologous memory CD4+ T cells...
May 2, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28459279/integrative-genomics-of-emphysema-associated-genes-reveals-potential-disease-biomarkers
#18
Ma'en Obeidat, Yunlong Nie, Nick Fishbane, Xuan Li, Yohan Bossé, Philippe Joubert, David C Nickle, Ke Hao, Dirkje S Postma, Wim Timens, Marc A Sze, Casey P Shannon, Zsuzsanna Hollander, Raymond T Ng, Bruce McManus, Bruce E Miller, Stephen Rennard, Avrum Spira, Tillie Louise Hackett, Wan Lam, Stephen Lam, Rosa Faner, Alvar Agusti, James C Hogg, Don D Sin, Peter D Paré
RATIONALE: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. Gene expression profiling across multiple regions of the same lung identified genes significantly related to emphysema. OBJECTIVE: To determine whether the lung and epithelial expression of 127 emphysema-related genes is also related to lung function in independent cohorts and whether any of these genes could be used as biomarkers in the peripheral blood of COPD patients...
May 1, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28445073/plasminogen-activator-inhibitor-1-is-critical-in-alcohol-enhanced-acute-lung-injury-in-mice
#19
Lauren G Poole, Veronica L Massey, Deanna L Siow, Edilson Torres-González, Nikole L Warner, James P Luyendyk, Jeffrey D Ritzenthaler, Jesse Roman, Gavin E Arteel
RATIONALE: Chronic alcohol exposure is a clinically important risk factor for development of acute respiratory distress syndrome, the most severe form of acute lung injury (ALI). However, the mechanisms by which alcohol sensitizes the lung to development of this disease are poorly understood. OBJECTIVES: We determined the role of the anti-fibrinolytic protein plasminogen activator inhibitor-1 (PAI-1) in alcohol enhancement of experimental endotoxin-induced ALI. METHODS: Wild-type (WT), PAI-1(-/-) and Integrin β3(-/-) mice were fed ethanol-containing Lieber-DeCarli liquid or control diet for 6 weeks followed by systemic lipopolysaccharide (LPS) challenge...
April 26, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28443685/lymphatic-changes-in-respiratory-diseases-more-than-just-remodeling-of-the-lung
#20
Benjamin Stump, Ye Cui, Pranav Kidambi, Anthony M Lamattina, Souheil El-Chemaly
Advances in our ability to identify lymphatic endothelial cells and differentiate them from blood endothelial cells have led to important progress in the study of lymphatic biology. Over the past decade, pre-clinical and clinical studies have shown that there are changes to the lymphatic vasculature in nearly all lung diseases. Efforts to understand the contribution of lymphatics and their growth factors to disease initiation, progression and resolution have led to seminal findings establishing critical roles for lymphatics in lung biology spanning from the first breath after birth to asthma, tuberculosis, and lung transplantation...
April 26, 2017: American Journal of Respiratory Cell and Molecular Biology
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