keyword
https://read.qxmd.com/read/38487999/mast-cell-activation-disrupts-interactions-between-endothelial-cells-and-pericytes-during-early-life-allergic-asthma
#1
JOURNAL ARTICLE
Régis Joulia, Franz Puttur, Helen Stölting, William J Traves, Lewis J Entwistle, Anastasia Voitovich, Minerva Garcia Martín, May Al-Sahaf, Katie Bonner, Elizabeth Scotney, Philip L Molyneaux, Richard J Hewitt, Simone A Walker, Laura Yates, Sejal Saglani, Clare M Lloyd
Allergic asthma generally starts during early life and is linked to substantial tissue remodeling and lung dysfunction. Although angiogenesis is a feature of the disrupted airway, the impact of allergic asthma on the pulmonary microcirculation during early life is unknown. Here, using quantitative imaging in precision-cut lung slices (PCLSs), we report that exposure of neonatal mice to house dust mite (HDM) extract disrupts endothelial cell/pericyte interactions in adventitial areas. Central to the blood vessel structure, the loss of pericyte coverage was driven by mast cell (MC) proteases, such as tryptase, that can induce pericyte retraction and loss of the critical adhesion molecule N-cadherin...
March 15, 2024: Journal of Clinical Investigation
https://read.qxmd.com/read/38361030/the-breathtaking-world-of-human-respiratory-in-vitro-models-investigating-lung-diseases-and-infections-in-3d-models-organoids-and-lung-on-chip
#2
REVIEW
Stefanie Dichtl, Wilfried Posch, Doris Wilflingseder
The COVID-19 pandemic illustrated an urgent need for sophisticated, human tissue models to rapidly test and develop effective treatment options against this newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, in particular, the last 3 years faced an extensive boost in respiratory and pulmonary model development. Nowadays, 3D models, organoids and lung-on-chip, respiratory models in perfusion, or precision-cut lung slices are used to study complex research questions in human primary cells...
February 15, 2024: European Journal of Immunology
https://read.qxmd.com/read/37987780/exogenous-hydrogen-sulfide-attenuates-hyperoxia-effects-on-neonatal-mouse-airways
#3
JOURNAL ARTICLE
Colleen M Bartman, Marta Schiliro, Lisa Nesbitt, Kenge K Lee, Y S Prakash, Christina M Pabelick
Supplemental O2 remains a necessary intervention for many premature infants (<34 weeks gestation). Even moderate hyperoxia (<60% O2 ) poses a risk for subsequent airway disease, thereby predisposing premature infants to pediatric asthma involving chronic inflammation, airway hyperresponsiveness (AHR), airway remodeling, and airflow obstruction. Moderate hyperoxia promotes AHR via effects on airway smooth muscle (ASM), a cell type that also contribute to impaired bronchodilation and remodeling (proliferation, altered extracellular matrix)...
November 21, 2023: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/37928904/the-rna-binding-proteins-zfp36l1-and-zfp36l2-are-dysregulated-in-airway-epithelium-in-human-and-a-murine-model-of-asthma
#4
JOURNAL ARTICLE
Jennifer Rynne, Elena Ortiz-Zapater, Dustin C Bagley, Onofrio Zanin, George Doherty, Varsha Kanabar, Jon Ward, David J Jackson, Maddy Parsons, Jody Rosenblatt, Ian M Adcock, Rocio T Martinez-Nunez
Introduction: Asthma is the most common chronic inflammatory disease of the airways. The airway epithelium is a key driver of the disease, and numerous studies have established genome-wide differences in mRNA expression between health and asthma. However, the underlying molecular mechanisms for such differences remain poorly understood. The human TTP family is comprised of ZFP36, ZFP36L1 and ZFP36L2, and has essential roles in immune regulation by determining the stability and translation of myriad mRNAs encoding for inflammatory mediators...
2023: Frontiers in Cell and Developmental Biology
https://read.qxmd.com/read/37907918/amitriptyline-inhibits-bronchoconstriction-and-directly-promotes-dilatation-of-the-airways
#5
JOURNAL ARTICLE
Paulina Hempel, Virag Klein, Anna Michely, Svenja Böll, Annette D Rieg, Jan Spillner, Till Braunschweig, Saskia von Stillfried, Norbert Wagner, Christian Martin, Klaus Tenbrock, Eva Verjans
INTRODUCTION: The standard therapy for bronchial asthma consists of combinations of acute (short-acting ß2 -sympathomimetics) and, depending on the severity of disease, additional long-term treatment (including inhaled glucocorticoids, long-acting ß2 -sympathomimetics, anticholinergics, anti-IL-4R antibodies). The antidepressant amitriptyline has been identified as a relevant down-regulator of immunological TH 2-phenotype in asthma, acting-at least partially-through inhibition of acid sphingomyelinase (ASM), an enzyme involved in sphingolipid metabolism...
October 31, 2023: Respiratory Research
https://read.qxmd.com/read/37523713/pro-relaxant-ep-receptors-functionally-partition-to-different-pro-contractile-receptors-in-airway-smooth-muscle
#6
JOURNAL ARTICLE
Ajay P Nayak, Elham Javed, Dominic R Villalba, Yinna Wang, Henry P Morelli, Sushrut D Shah, Nicholas Kim, Rennolds S Ostrom, Reynold A Panettieri, Steven S An, Dale D Tang, Raymond B Penn
Prostaglandin E2 (PGE2 ) imparts diverse physiological effects on multiple airway cells through its actions on four distinct E-type prostanoid (EP) receptors (EP1-4). Gs-coupled EP2 and EP4 receptors are expressed on airway smooth muscle (ASM), yet their capacity to regulate ASM contractile state remains subject to debate. We used EP2 (ONO-259) and EP4 (ONO-329) subtype-specific agonists in cell- and tissue- based models of human ASM contraction (Magnetic Twisting Cytometry (MTC), and precision cut lung slices (PCLS), respectively) to study the EP2- and EP4- regulation of ASM contraction and signaling under conditions of histamine or methacholine (MCh) stimulation...
July 31, 2023: American Journal of Respiratory Cell and Molecular Biology
https://read.qxmd.com/read/37448802/desert-particulate-matter-from-afghanistan-increases-airway-obstruction-in-human-distal-lungs-exposed-to-type-2-cytokine-il-13
#7
JOURNAL ARTICLE
Diana Cervantes, Niccolette Schaunaman, Gregory P Downey, Hong Wei Chu, Brian J Day
INTRODUCTION: Deployment related asthma-like symptoms including distal airway obstruction have been described in U.S. military personnel who served in Iraq and Afghanistan. The mechanisms responsible for the development of distal airway obstruction in deployers exposed to desert particulate matter (PM) is not well understood. We sought to determine if respiratory exposure to PM from Afghanistan (PMa) increases human distal airway hyperresponsiveness (AHR) with or without exposures to IL-13, a type 2 cytokine...
2023: Frontiers in Medicine
https://read.qxmd.com/read/37346175/inherent-differences-of-small-airway-contraction-and-ca-2-oscillations-in-airway-smooth-muscle-cells-between-balb-c-and-c57bl-6-mouse-strains
#8
JOURNAL ARTICLE
Zijian Zeng, Mengxin Cheng, Meng Li, Tao Wang, Fuqiang Wen, Michael J Sanderson, James Sneyd, Yongchun Shen, Jun Chen
BALB/c and C57BL/6 mouse strains are widely used as animal model in studies of respiratory diseases, such as asthma. Asthma is characterized by airway hyperresponsiveness, which is eventually resulted from the excessive airway smooth muscle (ASM) contraction mediated by Ca2+ oscillations in ASM cells. It is reported that BALB/c mice have inherently higher airway responsiveness, but show no different contractive response of tracheal ring as compared to C57BL/6 mice. However, whether the different airway responsiveness is due to the different extents of small airway contraction, and what's underlying mechanism remains unknown...
2023: Frontiers in Cell and Developmental Biology
https://read.qxmd.com/read/37098126/rhinovirus-c15-attenuates-relaxation-and-camp-production-in-human-airways-and-smooth-muscle
#9
JOURNAL ARTICLE
Eric B Gebski, Vishal Parikh, Hong Lam, Nicholas Kim, Yury Bochkov, Gaoyuan Cao, Reynold A Panettieri, Richard Kurten, James Gern, Steven S An, Cynthia J Koziol-White
Rhinoviruses (RV) evoke up to 85% of acute asthma exacerbations in children, 50% in adults, and can induce airway hyperresponsiveness and decrease efficacy of current therapeutics to provide symptom relief. Utilizing human precision cut lung slices (hPCLS), primary human air-liquid interface differentiated airway epithelial cells (HAEC), and human airway smooth muscle (HASM) as pre-clinical experimental models, we demonstrated that RV-C15 attenuates agonist-induced bronchodilation. Specifically, airway relaxation to formoterol and cholera toxin, but not forskolin, was attenuated following hPCLS exposure to RV-C15...
April 25, 2023: American Journal of Respiratory Cell and Molecular Biology
https://read.qxmd.com/read/37098022/calcium-sensing-receptor-negative-allosteric-modulators-oppose-contraction-of-mouse-airways
#10
JOURNAL ARTICLE
Jiayin Diao, Maggie Lam, Karen J Gregory, Katie Leach, Jane E Bourke
Asthma is a heterogeneous chronic airways disease with an unmet need for improved therapeutics in uncontrolled severe disease. The calcium-sensing receptor (CaSR) is a G protein-coupled receptor upregulated in asthma. The CaSR agonist, spermine, is also increased in asthmatic airways and contributes to bronchoconstriction. CaSR negative allosteric modulators (NAMs) oppose chronic airway inflammation, remodelling and hyperresponsiveness in murine and guinea pig asthma models, but whether CaSR NAMs are effective acute bronchodilators compared to standard-of-care has not yet been established...
April 25, 2023: American Journal of Respiratory Cell and Molecular Biology
https://read.qxmd.com/read/37008013/advances-in-respiratory-physiology-in-mouse-models-of-experimental-asthma
#11
REVIEW
Olivia R Carroll, Amber L Pillar, Alexandra C Brown, Min Feng, Hui Chen, Chantal Donovan
Recent advances in mouse models of experimental asthma coupled with vast improvements in systems that assess respiratory physiology have considerably increased the accuracy and human relevance of the outputs from these studies. In fact, these models have become important pre-clinical testing platforms with proven value and their capacity to be rapidly adapted to interrogate emerging clinical concepts, including the recent discovery of different asthma phenotypes and endotypes, has accelerated the discovery of disease-causing mechanisms and increased our understanding of asthma pathogenesis and the associated effects on lung physiology...
2023: Frontiers in Physiology
https://read.qxmd.com/read/36672178/the-bronchoprotective-effects-of-dual-pharmacology-muscarinic-receptor-antagonist-and-%C3%AE-2-adrenergic-receptor-agonist-navafenterol-in-human-small-airways
#12
JOURNAL ARTICLE
Joseph Antony Jude, Ian Dainty, Nikhil Karmacharya, William Jester, Reynold Panettieri
Bronchodilators and anti-inflammatory agents are the mainstream treatments in chronic obstructive and pulmonary disease (COPD) and asthma. The combination of β2 adrenergic receptor (β2 AR) agonists and muscarinic antagonists shows superior bronchoprotective effects compared to these agents individually. Navafenterol (AZD8871) is a single-molecule, dual pharmacology agent combining muscarinic antagonist and β2 AR agonist functions, currently in development as a COPD therapeutic. In precision-cut human lung slices (hPCLS), we investigated the bronchoprotective effect of navafenterol against two non-muscarinic contractile agonists, histamine and thromboxane A2 (TxA2 ) analog (U46619)...
January 6, 2023: Cells
https://read.qxmd.com/read/36662576/a-par3-lim-kinase-cofilin-pathway-mediates-human-airway-smooth-muscle-relaxation-by-tas2r14
#13
JOURNAL ARTICLE
Jung-A A Woo, Maria Castaño, Teresa R Kee, Jordan Lee, Cynthia J Koziol-White, Steven S An, Donghwa Kim, David E Kang, Stephen B Liggett
Bitter taste receptors (TAS2Rs) are G protein-coupled receptors expressed on human airway smooth muscle (HASM) cells; when activated by receptor agonists they evoke marked airway relaxation. In both taste and HASM cells, TAS2Rs activate a canonical Gβγ mediated stimulation of Ca2+ release from intracellular stores by activation of phospholipase Cβ(PLCβ). Alone, this [Ca2+ ]i signaling does not readily account for relaxation, particularly since bronchoconstrictive agonists acting at Gq coupled receptors also increase [Ca2+ ]i ...
January 20, 2023: American Journal of Respiratory Cell and Molecular Biology
https://read.qxmd.com/read/36634709/targeted-gata3-knockdown-in-activated-t-cells-via-pulmonary-sirna-delivery-as-novel-therapy-for-allergic-asthma
#14
JOURNAL ARTICLE
Rima Kandil, Domizia Baldassi, Sebastian Böhlen, Joschka T Müller, David C Keul, Tonia Bargmann, Susann Dehmel, Yuran Xie, Aditi Mehta, Katherina Sewald, Olivia M Merkel
GATA3 gene silencing in activated T cells displays a promising option to early-on undermine pathological pathways in the disease formation of allergic asthma. The central transcription factor of T helper 2 (Th2) cell cytokines IL-4, IL-5, and IL-13 plays a major role in immune and inflammatory cascades underlying asthmatic processes in the airways. Pulmonary delivery of small interfering RNAs (siRNA) to induce GATA3 knockdown within disease related T cells of asthmatic lungs via RNA interference (RNAi) presents an auspicious base to realize this strategy, however, still faces some major hurdles...
January 9, 2023: Journal of Controlled Release
https://read.qxmd.com/read/36227725/starving-a-cell-promotes-airway-smooth-muscle-relaxation-inhibition-of-glycolysis-attenuates-excitation-contraction-coupling
#15
JOURNAL ARTICLE
Shengjie Xu, Nikhil Karmacharya, Joanna Woo, Gaoyuan Cao, Changjiang Guo, Andrew Gow, Reynold A Panettieri, Joseph A Jude
Bronchomotor tone modulated by airway smooth muscle shortening represents a key mechanism that increases airway resistance in asthma. Altered glucose metabolism in inflammatory and airway structural cells is associated with asthma. Although these observations suggest a causal link between glucose metabolism and airway hyperresponsiveness (AHR), the mechanisms are unclear. We hypothesized that glycolysis modulates excitation-contraction (EC) coupling in human airway smooth muscle (HASM) cells. Cultured HASM cells from human lung donors were subject to metabolic screenings using Seahorse XF cell assay...
October 13, 2022: American Journal of Respiratory Cell and Molecular Biology
https://read.qxmd.com/read/36126785/spray-drying-sirna-lipid-nanoparticles-for-dry-powder-pulmonary-delivery
#16
JOURNAL ARTICLE
Christoph M Zimmermann, Domizia Baldassi, Karen Chan, Nathan B P Adams, Alina Neumann, Diana Leidy Porras-Gonzalez, Xin Wei, Nikolaus Kneidinger, Mircea Gabriel Stoleriu, Gerald Burgstaller, Dominik Witzigmann, Paola Luciani, Olivia M Merkel
While all the siRNA drugs on the market target the liver, the lungs offer a variety of currently undruggable targets which could potentially be treated with RNA therapeutics. Hence, local, pulmonary delivery of RNA nanoparticles could finally enable delivery beyond the liver. The administration of RNA drugs via dry powder inhalers offers many advantages related to physical, chemical and microbial stability of RNA and nanosuspensions. The present study was therefore designed to test the feasibility of engineering spray dried lipid nanoparticle (LNP) powders...
September 17, 2022: Journal of Controlled Release
https://read.qxmd.com/read/35841089/platelet-derived-growth-factor-pdgf-bb-regulates-the-airway-tone-via-activation-of-map2k-thromboxane-actin-polymerisation-and-ca-2-sensitisation
#17
JOURNAL ARTICLE
Annette D Rieg, Said Suleiman, Carolin Anker, Nina A Bünting, Eva Verjans, Jan Spillner, Sebastian Kalverkamp, Saskia von Stillfried, Till Braunschweig, Stefan Uhlig, Christian Martin
BACKGROUND: PDGFR-inhibition by the tyrosine kinase inhibitor (TKI) nintedanib attenuates the progress of idiopathic pulmonary fibrosis (IPF). However, the effects of PDGF-BB on the airway tone are almost unknown. We studied this issue and the mechanisms beyond, using isolated perfused lungs (IPL) of guinea pigs (GPs) and precision-cut lung slices (PCLS) of GPs and humans. METHODS: IPL: PDGF-BB was perfused after or without pre-treatment with the TKI imatinib (perfused/nebulised) and its effects on the tidal volume (TV), the dynamic compliance (Cdyn) and the resistance were studied...
July 15, 2022: Respiratory Research
https://read.qxmd.com/read/35776523/imidazobenzodiazepine-pi320-relaxes-mouse-peripheral-airways-by-inhibiting-calcium-mobilization
#18
JOURNAL ARTICLE
Jose F Perez-Zoghbi, Dannah Rae Sajorda, Daniel A Webb, Leggy A Arnold, Charles W Emala, Gene T Yocum
Asthma is a common respiratory disease characterized, in part, by excessive airway smooth muscle (ASM) contraction (airway hyperresponsiveness, AHR). Various γ-aminobutyric acid type A receptor (GABAA R) activators, including benzodiazepines, relax ASM. The GABAA R is a ligand-operated Cl- channel best known for its role in inhibitory neurotransmission in the central nervous system. Although ASM cells express GABAA Rs, affording a seemingly logical site of action, the mechanism(s) by which GABAA R ligands relax ASM remains unclear...
July 1, 2022: American Journal of Respiratory Cell and Molecular Biology
https://read.qxmd.com/read/35771468/infection-of-human-precision-cut-lung-slices-with-the-influenza-virus
#19
JOURNAL ARTICLE
Katherina Sewald, Olga Danov
Viral infections are common causes of asthma exacerbations. To model these processes ex vivo, human precision-cut lung slices (PCLSs) can be used. Here we describe the infection of human PCLSs with the human influenza virus. We then provide methods to quantify the virus and reveal its localization within infected PCLSs and study consequences of infection, including cell death and production of cytokines, chemokine, and mucus. We also describe the stimulation of PCLSs with immune mediators such as pro-inflammatory tumor necrosis factor α (TNF-α)...
2022: Methods in Molecular Biology
https://read.qxmd.com/read/35771467/human-precision-cut-lung-slices-generation-of-and-measurement-of-contractility-and-relaxation-of-small-airways
#20
JOURNAL ARTICLE
Cynthia Koziol-White
Lung slices have been used since the mid-1990's to study various aspects of lung biology that include, but are not limited to, mechanisms of airway contraction and relaxation; the pulmonary immune response in the context of inflammatory diseases of the lung like asthma and chronic obstructive pulmonary disease; mast cell-mediated airway contractility and inflammation; modulation of airway cells following pathogen exposure; and consequences of environmental toxicant exposure. Here we describe the generation of human precision-cut lung slices (hPCLS) and measurement of contraction and relaxation of small airways within the slices...
2022: Methods in Molecular Biology
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