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American Journal of Respiratory Cell and Molecular Biology

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https://www.readbyqxmd.com/read/27875656/involvement-of-jnk-in-tnf%C3%AE-driven-remodelling
#1
Irene Mj Eurlings, Niki L Reynaert, Cheryl van de Wetering, Scott W Aesif, Evi M Mercken, Rafael de Cabo, Jos L van der Velden, Yvonne M Janssen-Heininger, Emiel F M Wouters, Mieke A Dentener
Lung tissue remodeling in chronic obstructive pulmonary disease (COPD) is characterized by airway wall thickening and/or emphysema. Although the bronchial and alveolar compartments are functionally independent entities, we recently showed comparable alterations in matrix composition comprised of decreased elastin content and increased collagen and hyaluronan contents of alveolar and small airway walls. Out of several animal models tested SPC-TNFα mice showed remodelling in alveolar and airway walls similar to what is observed in COPD patients...
November 22, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27870560/effect-of-prenatal-versus-postnatal-vitamin-d-deficiency-on-pulmonary-structure-and-function-in-mice
#2
Ammar Saadoon, Namasivayam Ambalavanan, Kurt Zinn, Ambika P Ashraf, Mark MacEwen, Teodora Nicola, Michelle V Fanucchi, William T Harris
Epidemiologic studies have linked gestational vitamin D deficiency to respiratory diseases, although mechanisms have not been defined. We hypothesized that antenatal vitamin D deficiency would impair airway development and alveolarization in a mouse model. We studied the effect of antenatal vitamin D deficiency by inducing vitamin D deficiency in pregnant mice and then compared lung development and function in their offspring to littermate controls. Postnatal vitamin D deficiency and sufficiency models from each group were also studied...
November 21, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27854516/evasion-of-neutrophil-extracellular-traps-by-respiratory-pathogens
#3
Daniel M L Storisteanu, Joanna M Pocock, Andrew S Cowburn, Jatinder K Juss, Angalee Nadesalingam, Victor Nizet, Edwin R Chilvers
The release of neutrophil extracellular traps (NETs) is a major immune mechanism intended to capture pathogens. These histone and protease-coated DNA structures are released by neutrophils in response to a variety of stimuli, including respiratory pathogens, and have been identified in the airways of patients with respiratory infection, cystic fibrosis, acute lung injury, primary graft dysfunction and COPD. NET production has been demonstrated in the lungs of mice infected with Staphylococcus aureus, Klebsiella pneumoniae and Aspergillus fumigatus...
November 17, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27854509/tgf-%C3%A3-1-function-in-airway-remodeling-and-hyperresponsiveness-the-missing-link
#4
Christie A Ojiaku, Edwin J Yoo, Reynold A Panettieri
The pathogenesis of asthma includes a complex interplay between airway inflammation, hyperresponsiveness, and remodeling. Current evidence suggests that airway structural cells - including bronchial smooth muscle cells, myofibroblasts, fibroblasts, and epithelial cells -mediate all three aspects of asthma pathogenesis. While studies show a connection between airway remodeling and changes in bronchomotor tone, the relationship between the two remains unclear. Transforming growth factor beta 1 (TGF-ß1), a growth factor elevated in the airway of patients with asthma, plays a role in airway remodeling and the shortening of various airway structural cells...
November 17, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27854507/sex-based-genetic-association-study-identifies-celsr1-as-a-possible-copd-risk-locus-among-women
#5
Megan Hardin, Michael H Cho, Sunita S Sharma, Kimberly Glass, Peter J Castaldi, Merry-Lynn McDonald, Hugues Aschard, Jody Senter-Sylvia, Kelan Tantisira, Scott T Weiss, Craig P Hersh, Jarrett D Morrow, David Lomas, Alvar Agusti, Per Bakke, Amund Gulsvik, George T O'Connor, Josée Dupuis, John Hokanson, James Crapo, Terri H Beaty, Nan Laird, Edwin K Silverman, Dawn L DeMeo
BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a complex disease with strong environmental and genetic influences and sexually dimorphic features. Although genetic risk factors for COPD have been identified, much of the heritability remains unexplained. Sex-based genetic association studies may uncover additional COPD genetic risk factors. METHODS: We studied current and former smokers from COPD case-control cohorts (COPDGene non-Hispanic whites and African Americans, ECLIPSE, and GenKOLS)...
November 17, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27814452/water-permeability-adjusts-resorption-in-lung-epithelia-to-increased-apical-surface-liquid-volumes
#6
Hanna Schmidt, Christiane Michel, Peter Braubach, Michael Fauler, Daniel Neubauer, Kristin E Thompson, Manfred Frick, Boris Mizaikoff, Paul Dietl, Oliver H Wittekindt
The apical surface liquid layer (ASL) covers the airways and forms a first line of defense against pathogens. Maintenance of ASL volume by airway epithelia is essential for maintaining lung function. The proteolytic activation of epithelial Na(+) channels (ENaC) is believed to be the dominating mechanism to cope with increases in ASL volumes. Alternative mechanisms, in particular increases in epithelial water permeability (Posm), have so far been regarded as rather less important. However, most studies mainly addressed immediate effects upon apical volume expansion (AVE) and increases in ASL...
November 4, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27805412/sod3-r213g-snp-blocks-murine-bleomycin-induced-fibrosis-and-promotes-resolution-of-inflammation
#7
Gary C Mouradian, Rohit Gaurav, Steve Pugliese, Karim El Kasmi, Brittany Hartman, Laura Hernandez-Lagunas, Kurt Stenmark, Russ P Bowler, Eva Nozik-Grayck
Loss of extracellular superoxide dismutase (SOD3) contributes to inflammatory and fibrotic lung diseases. The human SOD3 R213G polymorphism decreases matrix binding, redistributing SOD3 from the lung to extracellular fluids and protects against LPS induced alveolar inflammation. We utilized mice expressing a naturally occurring single nucleotide polymorphism (SNP), rs1799895, within the HBD of SOD3 which results in an amino acid substitution at position 213 (R213G mice) to test the hypothesis that the redistribution of SOD3 into the extracellular fluids would impart protection against bleomycin-induced lung fibrosis and secondary pulmonary hypertension (PH)...
November 2, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27788019/a-heterotopic-xenograft-model-of-human-airways-for-investigating-fibrosis-in-asthma
#8
Tillie-Louise Hackett, Sarah C Ferrante, Claire E Hoptay, John F Engelhardt, Jennifer L Ingram, Yulong Zhang, Sarah E Alcala, Furquan Shaheen, Ethan Matz, Dinesh K Pillai, Robert J Freishtat
Rationale - Limited in vivo models exist to investigate the lung airway epithelial role in repair, regeneration, and pathology of chronic lung diseases. Herein, we introduce a novel animal model in asthma - a xenograft system integrating a differentiating human asthmatic airway epithelium with an actively remodeling rodent mesenchyme in an immunocompromised murine host. Methods - Human asthmatic and non-asthmatic airway epithelial cells were seeded into decellularized rat tracheas. Tracheas were ligated to a sterile cassette and implanted subcutaneously in the flanks of nude mice...
October 27, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27788015/transcriptomic-analysis-reveals-significant-b-lymphocyte-suppression-in-corticosteroid-treated-hosts-with-pneumocystis-pneumonia
#9
Yang Hu, Dong Wang, Kan Zhai, Zhaohui Tong
Pneumocystis pneumonia (PCP) is an opportunistic infectious disease that is prevalent in immunosuppressed hosts. Corticosteroid treatment is the most significant risk factor for HIV-negative patients with PCP, although little is known about how corticosteroids alter the host defense against Pneumocystis infection. In the present study, we used transcriptome analysis to examine the immune response in the lungs of corticosteroid-treated PCP mice. The results showed downregulation in the genes related to both native immunity, such as antigen processing and presentation, inflammatory response, and phagocytosis, as well as B and T lymphocyte immunity...
October 27, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27780343/gene-editing-and-genetic-lung-disease-basic-research-meets-therapeutic-application
#10
Deepthi Alapati, Edward E Morrisey
While our understanding of the genetics and pathology of congenital lung diseases such as surfactant protein deficiency, cystic fibrosis and alpha 1 antitrypsin deficiency is extensive, treatment options are lacking. Since the lung is a barrier organ in direct communication with the external environment, targeted delivery of gene corrective technologies to the respiratory system via intra-tracheal or intranasal routes is an attractive option for therapy. CRISPR/Cas9 gene editing technology is a promising approach to repair or inactivate disease causing mutations...
October 25, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27779901/identification-and-characterization-of-a-dendritic-cell-precursor-in-parenchymal-lung-tissue
#11
Christophe von Garnier, Fabian Blank, Barbara Rothen-Rutishauser, Joachim R Goethert, Patrick G Holt, Philip A Stumbles, Deborah H Strickland
The pulmonary parenchymal and mucosal microenvironments are constantly exposed to the external environment and thus require continuous surveillance to maintain steady-state immunological homeostasis. This is achieved by a mobile network of pulmonary dendritic cells (DC) and macrophages (mø) that constantly sample and process microenvironmental antigens into signals that can initiate or dampen inflammation, either locally or after onward migration to draining lymph nodes. The constant steady-state turnover of pulmonary DC and mø requires replenishment from bone-marrow precursors, however the nature of the pulmonary precursor cell remains unclear, although recent studies suggest that subsets of pulmonary DC may derive from circulating monocytic precursors...
October 25, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27779900/ablation-of-pericyte-like-cells-in-lungs-by-oropharyngeal-aspiration-of-diphtheria-toxin
#12
Chi F Hung, Yu-Hua Chow, W Conrad Liles, William A Altemeier, Lynn M Schnapp
: We previously demonstrated that FoxD1-derived cells in the lung are enriched in pericyte-like cells in mouse lung. These cells express the common pericyte markers and are located adjacent to endothelial cells. In this study we demonstrate the feasibility of administering diphtheria toxin (DT) by oropharyngeal aspiration as an approach to ablate FoxD1-derived cells. METHOD: We crossed mice expressing Cre-recombinase under the FoxD1 promoter to Rosa26-loxP-STOP-loxP-iDTR mice and generated a bitransgenic line (FoxD1-Cre;Rs26-iDTR) where FoxD1-derived cells heritably express iDTR and are sensitive to DT...
October 25, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27767332/immune-regulation-of-tlr2-engagement-on-cd4-t-cells-in-murine-models-of-malignant-pleural-effusion
#13
Xiu-Zhi Wu, Qiong Zhou, Hua Lin, Kan Zhai, Xiao-Juan Wang, Wei-Bing Yang, Huan-Zhong Shi
RATIONALE: Toll like receptor (TLR) 2 is well known by sensing multiple ligands; however, its role in the development of malignant pleural effusion (MPE) remains unknown. We performed the present study to explore the impact of TLR2 signaling on the development of MPE, and to define the underline mechanisms by which TLR2 works. METHODS: Development of MPE was compared between TLR2-/- and wild type (WT) mice. The effect of TLR2 on differentiation of Th17, Th9, and Th2 cells in MPE was explored...
October 21, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27767327/lung-dendritic-cells-shaping-immune-responses-throughout-copd-progression
#14
Christine M Freeman, Jeffrey L Curtis
Hallmarks of chronic obstructive pulmonary disease (COPD) include innate inflammation and remodeling of small airways that begin in early disease and the development of lung lymphoid follicles (LLF), indicative of adaptive immunity, in more spirometrically-severe stages. Common to these processes in all stages is orchestration by dendritic cells (DC). Recently improved understanding of the analogous lung DC subsets in humans and mice has allowed for better integration and interpretation of the experimental and clinical pathological literature...
October 21, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27755915/platelet-specific-chemokines-contribute-to-the-pathogenesis-of-acute-lung-injury
#15
Khalil Bdeir, Kandace Gollomp, Marta Stasiak, Junjie Mei, Izabela Papiewska-Pajak, Guohua Zhao, G Scott Worthen, Douglas B Cines, Mortimer Poncz, M Anna Kowalska
RATIONALE: Platelets and neutrophils contribute to the development of acute lung injury (ALI). However, the mechanism by which platelets make this contribution is incompletely understood. We asked whether the two most abundant platelet chemokines, CXCL7, which induces neutrophil chemotaxis and activation, and CXCL4, which does neither, mediate ALI through complementary pathogenic pathways. OBJECTIVES: To examine the role of platelet-derived chemokines in the pathogenesis of ALI using Cxcl7-/- and Cxcl4-/- knockout mice and mice that express human CXCL7 or CXCL4...
October 18, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27749084/cross-species-transcriptome-profiling-identifies-new-alveolar-epithelial-type-i-cell-specific-genes
#16
Crystal N Marconett, Beiyun Zhou, Mitsuhiro Sunohara, Tiffany M Pouldar, HongJun Wang, Yixin Liu, Megan E Rieger, Evelyn Tran, Per Flodby, Kimberly D Siegmund, Edward D Crandall, Ite A Laird-Offringa, Zea Borok
Diseases involving the distal lung alveolar epithelium include chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and lung adenocarcinoma. Accurate labeling of specific cell types is critical for determining the contribution of each to pathogenesis of these diseases. The distal lung alveolar epithelium is comprised of two cell types, alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. While cell type-specific markers, most prominently surfactant protein C (SFTPC), have allowed detailed lineage tracing studies of AT2 cell differentiation and their roles in disease, studies of AT1 cells have been hampered by lack of genes with expression unique to AT1 cells...
October 17, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27710012/mechanistic-studies-of-capsaicin-induced-apnea-in-rodents
#17
Jun Ren, Xiuqing Ding, John J Greer
Inhalation of capsaicin based sprays can cause central respiratory depression and lethal apneas. There are contradictory reports regarding the sites of capsaicin action. Further, an understanding of the neurochemical mechanisms underlying capsaicin-induced apneas and the development of pharmacological interventions are lacking. The main objectives were to perform a systematic study of the mechanisms of action of capsaicin-induced apneas and to provide insights relevant to pharmacological intervention. In vitro and in vivo rat and TRPV1-null mouse models were used to measure respiratory parameters and seizure-like activity in the presence of capsaicin and compounds that modulate glutamatergic neurotransmission...
October 6, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27679954/ifn-%C3%AE-blocks-development-of-an-asthma-phenotype-in-rhinovirus-infected-baby-mice-by-inhibiting-ilc2s
#18
Mingyuan Han, Jun Young Hong, Suraj Jaipalli, Charu Rajput, Jing Lei, Joanna L Hinde, Qiang Chen, Natalie M Hershenson, J Kelley Bentley, Marc B Hershenson
Early-life wheezing-associated infections with rhinovirus (RV) have been associated with asthma development in children. We have shown that RV infection of six day-old mice induces mucous metaplasia and airways hyperresponsiveness which is dependent on IL-13, IL-25 and type 2 innate lymphoid cells (ILC2s). Infection of immature mice fails to induce lung IFN-γ expression, in contrast to mature 8 week-old mice with a robust IFN-γ response, consistent with the notion that deficient IFN-γ production in immature mice permits RV-induced type 2 immune responses...
September 28, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27668462/lrp5-%C3%AE-catenin-signaling-controls-lung-macrophage-differentiation-and-inhibits-resolution-of-fibrosis
#19
Joseph A Sennello, Alexander V Misharin, Annette S Flozak, Sergejs Berdnikovs, Paul Cheresh, John Varga, David W Kamp, G R Scott Budinger, Cara J Gottardi, Anna P Lam
Previous studies established that attenuating Wnt/β-catenin signaling limits lung fibrosis in the bleomycin mouse model of this disease, but the contribution of this pathway to distinct lung cell phenotypes relevant to tissue repair and fibrosis remains incompletely understood. Using microarray analysis, we found that bleomycin-injured lungs from mice that lack the Wnt co-receptor Lrp5 and exhibit reduced fibrosis, showed enrichment for pathways related to extracellular matrix processing, immunity, and lymphocyte proliferation, suggesting the contribution of an immune-matrix remodeling axis relevant to fibrosis...
September 26, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27668315/evaluation-of-lecithinized-superoxide-dismutase-for-prevention-of-acute-respiratory-distress-syndrome-in-animal-models
#20
Ken-Ichiro Tanaka, Fumiya Tamura, Toshifumi Sugizaki, Masahiro Kawahara, Keiji Kuba, Yumiko Imai, Tohru Mizushima
RATIONALE: For acute respiratory distress syndrome (ARDS), mechanical ventilation (MV) is a life-saving intervention without alternative, however, MV can cause ventilator-induced lung injury (VILI). Reactive oxygen species (ROS) play important roles in the pathogenesis of both ARDS and VILI. Lecithinized superoxide dismutase (PC-SOD) has overcome limitations of SOD such as low tissue affinity and low stability in plasma. OBJECTIVES: In this study, we have examined the effect of PC-SOD on tissue injury, edema and inflammation in the lung and other organs of mice subjected to cecal ligation and puncture (CLP), lipopolysaccharide (LPS) administration or MV...
September 26, 2016: American Journal of Respiratory Cell and Molecular Biology
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