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American Journal of Respiratory Cell and Molecular Biology

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https://www.readbyqxmd.com/read/28208028/early-life-wildfire-smoke-exposure-is-associated-with-immune-dysregulation-and-lung-function-decrements-in-adolescence
#1
Carolyn Black, Joan E Gerriets, Justin H Fontaine, Richart W Harper, Nicholas J Kenyon, Fern Tablin, Edward S Schelegle, Lisa A Miller
RATIONALE: The long-term health effects of wildfire smoke exposure in pediatric populations are not known. OBJECTIVE: To determine if early life exposure to wildfire smoke can affect parameters of immunity and airways physiology that are detectable with maturity. METHODS: We studied a mixed gender cohort of rhesus macaque monkeys that were exposed as infants to ambient wood smoke from a series of Northern California wildfires in the summer of 2008...
February 16, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28199134/genetic-control-of-fatty-acid-%C3%AE-oxidation-in-chronic-obstructive-pulmonary-disease
#2
Zhiqiang Jiang, Nelson H Knudsen, Gang Wang, Weiliang Qiu, Zun Zar Chi Naing, Yan Bai, Xingbin Ai, Chih-Hao Lee, Xiaobo Zhou
Bioenergetics homeostasis is important for cells to sustain normal functions and defend against injury. Genetics controls on bioenergetics homeostasis, especially lipid metabolism remain poorly understood in chronic obstructive pulmonary diseases (COPD), the third leading cause of death in the world. Additionally, biological function of most susceptible genes identified from genome-wide association studies (GWAS) in COPD remains unclear. Here, we aim to address 1) how fatty acid oxidation, specifically β-oxidation (FAO), a key lipid metabolism pathway that provides energy to cells, contributes to cigarette smoke (CS)-induced COPD; and 2) whether and how FAM13A (family with sequence similarity 13 member A), a well-replicated COPD GWAS gene, modulates FAO pathway...
February 15, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28187270/epithelial-myeloid-differentiation-factor-88-is-dispensable-during-klebsiella-pneumonia
#3
Adam A Anas, Theodora A M Claushuis, Rajiv A Mohan, Vincent M Christoffels, Vassilis Aidinis, Sandrine Florquin, Cornelis Van't Veer, Baidong Hou, Alex F de Vos, Tom van der Poll
Klebsiella (K.) pneumoniae is a common cause of pneumonia. Previous studies have documented an important role for Toll-like receptors (TLRs) expressed by myeloid cells in the recognition of K. pneumoniae and the initiation of a protective immune response. Lung epithelial cells also express TLRs and can participate in innate immune defense. The aim of this study was to examine the role of the common TLR adaptor protein myeloid differentiation factor (MyD)88 in lung epithelium during host defense against K. pneumoniae induced pneumonia...
February 10, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28187268/fibroblast-growth-factor-signaling-mediates-pulmonary-endothelial-glycocalyx-reconstitution
#4
Yimu Yang, Sarah M Haeger, Matthew A Suflita, Fuming Zhang, Kyrie L Dailey, James F Colbert, Joshay A Ford, Mario A Picon, Robert S Stearman, Lei Lin, Xinyue Liu, Xiaorui Han, Robert J Linhardt, Eric P Schmidt
RATIONALE: The endothelial glycocalyx is a heparan sulfate-rich endovascular structure critical to endothelial function. Accordingly, endothelial glycocalyx degradation during sepsis contributes to tissue edema and organ injury. OBJECTIVE: We determined the endogenous mechanisms governing pulmonary endothelial glycocalyx reconstitution, and if these reparative mechanisms are impaired during sepsis. METHODS: We performed intravital microscopy of wild-type and transgenic mice to determine the rapidity of pulmonary endothelial glycocalyx reconstitution after non-septic (heparinase-III-mediated) or septic (cecal ligation and puncture-mediated) endothelial glycocalyx degradation...
February 10, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28170284/genetic-association-and-risk-scores-in-a-copd-meta-analysis-of-16-707-subjects
#5
Robert Busch, Brian D Hobbs, Jin Zhou, Peter J Castaldi, Michael J McGeachie, Megan E Hardin, Iwona Hawrylkiewicz, Pawel Sliwinski, Jae-Joon Yim, Woo Jin Kim, Deog K Kim, Alvar Agusti, Barry J Make, James D Crapo, Peter M Calverley, Claudio F Donner, David A Lomas, Emiel F M Wouters, Jørgen Vestbo, Ruth Tal-Singer, Per Bakke, Amund Gulsvik, Augusto A Litonjua, David Sparrow, Peter D Paré, Robert D Levy, Stephen I Rennard, Terri H Beaty, John Hokanson, Edwin K Silverman, Michael H Cho
The heritability of chronic obstructive pulmonary disease (COPD) cannot be fully explained by recognized genetic risk factors identified as achieving genome-wide significance. In addition, the combined contribution of genetic variation to COPD risk has not been fully explored. We sought to determine 1) whether studies of variants from previous studies of COPD or lung function in a larger sample could identify additional associated variants, particularly for severe COPD, and 2) the impact of genetic risk scores on COPD...
February 7, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28157452/activated-%C3%AE-2-integrins-restrict-neutrophil-recruitment-during-murine-acute-pseudomonal-pneumonia
#6
Zachary S Wilson, Lawrence B Ahn, William S Serratelli, Matthew D Belley, Joanne Lomas-Neira, Mehmet Sen, Craig T Lefort
Rapid neutrophil recruitment is critical for the efficient clearance of bacterial pathogens from the lungs. While β2 integrins and their activation are required for neutrophil recruitment from postcapillary venules of the systemic circulation into inflamed tissues, the involvement of integrins in neutrophil recruitment in response to respiratory infection varies between bacterial pathogens. For stimuli eliciting β2 integrin-dependent neutrophil influx, including Pseudomonas aeruginosa, it remains unclear whether the activation of β2 integrins is an essential step in this process...
February 3, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28157451/the-role-of-nod-like-receptors-in-pulmonary-infection
#7
Kristin M Wiese, Bria M Coates, Karen M Ridge
Pneumonia is caused by both viral and bacterial pathogens and is responsible for a significant health burden in the Unites States. The innate immune system is the human body's first line of defense against these pathogens. The recognition of invading pathogens via pattern recognition receptors (PRRs) leads to proinflammatory cytokine and chemokine production followed by recruitment and activation of effector immune cells. The nonspecific inflammatory nature of the innate immune response can result in immunopathology that is detrimental to the host...
February 3, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28145731/coupling-of-airway-smooth-muscle-tas2rs-to-intracellular-signaling-and-relaxation-is-via-g%C3%AE-i1-2-3
#8
Donghwa Kim, Jung A Woo, Ezekiel Geffken, Steven S An, Stephen B Liggett
Bitter taste receptors (TAS2Rs) are expressed on human airway smooth muscle (HASM) and evoke marked relaxation. Agonist interaction with TAS2Rs activates PLC and increases compartmentalized [Ca(2+)]i via IP3. In taste cells, the G-protein gustducin couples TAS2R to PLC, however we find very low levels of Gαgust mRNA or protein in HASM. We hypothesized that another G-protein in HASM transmits TAS2R function. TAS2R signaling to [Ca(2+)]i, ERK1/2, and physiologic relaxation was sensitive to pertussis toxin confirming a role for a member of the Gi-family...
February 1, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28135421/hypoxia-sensing-and-persistence-genes-are-expressed-during-the-intra-granulomatous-survival-of-m-tuberculosis
#9
Teresa A Hudock, Taylor W Foreman, Nirmalya Bandyopadhyay, Uma S Gautam, Ashley Veatch, Denae N LoBato, Kaylee M Gentry, Nadia A Golden, Amy Cavigli, Michelle Mueller, Shen-An Hwang, Robert L Hunter, Xavier Alvarez, Andrew A Lackner, Joel S Bader, Smriti Mehra, Deepak Kaushal
BACKGROUND: While it is accepted that the environment within the granuloma profoundly affects Mycobacterium tuberculosis (Mtb) and infection outcome, our ability to understand Mtb gene expression in these niches has been limited. We determined intragranulomatous gene expression in human like lung lesions derived from nonhuman primates with both active (ATB) and latent (LTBI) tuberculosis. METHODS: We employed a non-laser based approach to micro-dissect individual lung lesions and interrogate the global transcriptome of Mtb within granulomas...
January 30, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28129517/postnatal-hyperoxia-exposure-durably-impairs-right-ventricular-function-and-mitochondrial-biogenesis
#10
Kara N Goss, Santosh Kumari, Laura H Tetri, Greg Barton, Rudolph K Braun, Timothy A Hacker, Marlowe W Eldridge
RATIONALE: Prematurity complicates 12% of births, and young adults with a history of prematurity are at risk to develop right ventricular hypertrophy and impairment. The long-term risk for pulmonary vascular disease, as well as mechanisms of right ventricular dysfunction and ventricular-vascular uncoupling following prematurity remain poorly defined. METHODS: Using an established model of prematurity related lung disease, pups from timed-pregnant Sprague Dawley rats were randomized to normoxia or hyperoxia (FIO2 0...
January 27, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28125278/roles-for-the-cx3cl1-cx3cr1-and-ccl2-ccr2-chemokine-systems-in-hypoxic-pulmonary-hypertension
#11
Valérie Amsellem, Shariq Abid, Lucie Poupel, Aurélien Parpaleix, Mathieu Rodero, Guillaume Gary-Bobo, Mehdi Latiri, Jean-Luc Dubois-Rande, Larissa Lipskaia, Christophe Combadiere, Serge Adnot
Monocytes/macrophages are major effectors of lung inflammation associated with various forms of pulmonary hypertension (PH). Interactions between the CCL2/CCR2 and CX3CL1/CX3CR1 chemokine systems that guide phagocyte infiltration are incompletely understood. Our objective was to explore the individual and combined actions of CCL2/CCR2 and CX3CL1/CX3CR1 in hypoxia-induced PH in mice, particularly their roles in monocyte trafficking, macrophage polarization, and pulmonary vascular remodeling. The development of hypoxia-induced PH was associated with marked increases in lung levels of CX3CR1, CCR2, and their respective ligands CX3CL1 and CCL2...
January 26, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28125268/multipotent-myoepithelial-progenitor-cells-are-born-early-during-airway-submucosal-gland-development
#12
Preston J Anderson, Thomas J Lynch, John F Engelhardt
Airway submucosal glands (SMGs) are facultative stem cell niches for the surface epithelium, but the phenotype of the SMG-derived progenitor cells remains unclear. In other organs, glandular myoepithelial cells (MECs) have been proposed to be multipotent progenitors for luminal cells. We sought to determine the developmental phase during which mouse tracheal glandular MECs are born and whether these MECs are progenitors for other cell phenotypes during SMG morphogenesis. To approach this question, we localized two MEC protein markers (α-smooth muscle actin [αSMA/ACTA2] and smooth muscle myosin heavy chain 11 [SMMHC/MYH11]) during various stages of SMG development (placode, elongation, branching, and differentiation) and used ACTA2-CreERT2 and MYH11-CreERT2 transgenic mice to fate map MEC-derived lineages during SMG morphogenesis...
January 26, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28118027/impaired-relaxation-of-airway-smooth-muscle-in-mice-lacking-the-actin-binding-protein-gelsolin
#13
Maya Mikami, Yi Zhang, Jennifer Danielsson, Tiarra Joell, Hwan Mee Yong, Elizabeth Townsend, Seema Khurana, Steven S An, Charles W Emala
Diverse classes of ligands have recently been discovered that relax airway smooth muscle (ASM) despite a transient increase in intracellular calcium concentrations ([Ca(2+)]i). However, the cellular mechanisms are not well understood. Gelsolin is a calcium-activated actin severing and capping protein found in many cell types including ASM cells. Gelsolin also binds to phosphatidylinositol 4,5-bisphosphate (PIP2) making this substrate less available for phospholipase Cβ-mediated hydrolysis to inositol triphosphate (IP3) and diacylglycerol...
January 24, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28118023/il-17a-blockade-attenuates-obliterative-bronchiolitis-and-ifn%C3%AE-cellular-immune-response-in-lung-allografts
#14
Pawan Kumar Gupta, Sarah R Wagner, Qiang Wu, Rebecca A Shilling
Obliterative bronchiolitis (OB), characterized by fibrous obliteration of the small airways, is a major impediment to long-term survival in lung transplant recipients. We have previously found that IL-17A is primarily produced by CD4+ T cells and γδ T cells after lung transplant in a mouse model of orthotopic lung transplant. Absence of either subset of T cells was compensated for by expansion of the other subset, which suggested systemic blockade of IL-17A was necessary. To determine the specific role of IL-17A in the development of OB, we treated lung allograft recipients with an IL-17A antagonistic antibody...
January 24, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28118022/development-of-a-mouse-model-of-metabolic-syndrome-pulmonary-hypertension-and-heart-failure-with-preserved-ejection-fraction-ph-hfpef
#15
Qingqing Meng, Yen-Chun Lai, Neil J Kelly, Marta Bueno, Jeffrey Baust, Timothy Bachman, Dmitry Goncharov, Rebecca R Vanderpool, Josiah E Radder, Jian Hu, Elena Goncharova, Alison Morris, Ana L Mora, Steven D Shapiro, Mark T Gladwin
RATIONALE: Pulmonary hypertension associated with heart failure and preserved ejection fraction (PH-HFpEF; WHO Group II) secondary to left ventricular diastolic dysfunction is the most frequent cause of pulmonary hypertension. It is an increasingly recognized clinical complication of the metabolic syndrome. To date, no effective treatment has been identified and no genetically modifiable mouse model is available for advancing our understanding for PH-HFpEF. METHODS AND MAIN RESULTS: To develop a mouse model of PH-HFpEF, we exposed 36 mouse strains to 20 weeks of high-fat diet (HFD), followed by systematic evaluation of right and left ventricular pressure-volume analysis...
January 24, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28107636/visceral-white-adipose-tissue-following-chronic-intermittent-and-sustained-hypoxia-in-mice
#16
David Gozal, Alex Gileles-Hillel, Rene Cortese, Yan Li, Isaac Almendros, Zhuanhong Qiao, Ahamed A Khalyfa, Jorge Andrade, Abdelnaby Khalyfa
BACKGROUND: Angiogenesis, a process induced by hypoxia in visceral white adipose tissue (vWAT) in the context of obesity, mediates obesity-induced metabolic dysfunction and insulin resistance. Chronic intermittent hypoxia (IH) and sustained hypoxia (SH) induce body weight reductions and insulin resistance of differing magnitude, suggesting different HIF-1α-related activity. METHODS: 8-week old male C57BL/6J mice (n=10-12/group) were exposed to either IH, SH,or room air (RA)...
January 20, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28085510/age-dependent-changes-of-ampk-metabolic-pathways-in-the-lung-in-a-mouse-model-of-hemorrhagic-shock
#17
Lindsey R Klingbeil, Paul Kim, Giovanna Piraino, Michael O'Connor, Paul W Hake, Vivian Wolfe, Basilia Zingarelli
RATIONALE: The development of multiple organ failure in patients with hemorrhagic shock is significantly impacted by the patient age. AMP-activated protein kinase (AMPK) is a crucial regulator of energy homeostasis, which coordinates metabolic repair during cellular stress. OBJECTIVES: We investigated whether AMPK-regulated signaling pathways are age-dependent in hemorrhage-induced lung injury and whether AMPK activation by 5-amino-4-imidazole carboxamide riboside (AICAR) affords lung protective effects...
January 13, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28085498/mouse-genome-wide-association-study-of-pre-clinical-group-ii-pulmonary-hypertension-identifies-egfr
#18
Neil J Kelly, Josiah E Radder, Jeffrey J Baust, Christine L Burton, Yen-Chun Lai, Karin C Potoka, Brittani A Agostini, John P Wood, Timothy N Bachman, Rebecca R Vanderpool, Nadine Dandachi, Adriana S Leme, Alyssa D Gregory, Alison Morris, Ana L Mora, Mark T Gladwin, Steven D Shapiro
RATIONALE: Pulmonary hypertension (PH) is associated with features of obesity and metabolic syndrome that translate to the induction of PH by chronic high-fat diet (HFD) in some inbred mouse strains. We conducted a genome-wide association study (GWAS) to identify candidate genes associated with susceptibility to HFD-induced PH. METHODS: Mice from 36 inbred and wild-derived strains were fed with regular diet (RD) or HFD for 20 weeks beginning at 6-12 weeks of age after which right ventricular (RV) and left ventricular (LV) end-systolic pressure (ESP) and maximum pressure (MaxP) were measured by cardiac catheterization...
January 13, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28085493/metabolism-and-skeletal-muscle-homeostasis-in-lung-disease
#19
Ermelinda Ceco, Samuel E Weinberg, Navdeep S Chandel, Jacob I Sznajder
There is increased awareness that patients with lung diseases develop muscle dysfunction. Muscle dysfunction is a major contributor to a decreased quality of life in patients with chronic pulmonary diseases. Furthermore, muscle dysfunction exacerbates lung disease outcome, as a decrease in muscle mass and function are associated with increased morbidity, often long after critical illness or lung disease has been resolved. As we are learning more about the role of metabolism in health and disease, we are appreciating more the direct role of metabolism in skeletal muscle homeostasis...
January 13, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28080134/alveolar-epithelial-cell-derived-mediators-potential-direct-regulators-of-large-airway-and-vascular-responses
#20
Elizabeth A Oczypok, Timothy N Perkins, Tim D Oury
Bronchial epithelial cells and pulmonary endothelial cells are thought to be the primary modulators of conducting airways and vessels, respectively. However, histological examination of both mouse and human lung tissue reveals that alveolar epithelial cells (AECs) line the adventitia of large airways and vessels and thus are also in a position to directly regulate these structures. The primary purpose of this perspective is to highlight that AECs coat the adventitial surface of every vessel and airway in the lung parenchyma...
January 12, 2017: American Journal of Respiratory Cell and Molecular Biology
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