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Precision cut lung slice, asthma

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https://www.readbyqxmd.com/read/29760450/caveolin-3-differentially-orchestrates-cholinergic-and-serotonergic-constriction-of-murine-airways
#1
M Keshavarz, M Skill, M I Hollenhorst, S Maxeiner, M Walecki, U Pfeil, W Kummer, G Krasteva-Christ
The mechanisms of controlling airway smooth muscle (ASM) tone are of utmost clinical importance as inappropriate constriction is a hallmark in asthma and chronic obstructive pulmonary disease. Receptors for acetylcholine and serotonin, two relevant mediators in this context, appear to be incorporated in specialized, cholesterol-rich domains of the plasma membrane, termed caveolae due to their invaginated shape. The structural protein caveolin-1 partly accounts for anchoring of these receptors. We here determined the role of the other major caveolar protein, caveolin-3 (cav-3), in orchestrating cholinergic and serotonergic ASM responses, utilizing newly generated cav-3 deficient mice...
May 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29493871/montelukast-reverses-airway-remodeling-in-actively-sensitized-young-mice
#2
Stephane Debelleix, Valérie Siao-Him Fa, Hugues Begueret, Patrick Berger, Andy Kamaev, Olga Ousova, Roger Marthan, Michael Fayon
Asthma is characterized by airway hyperresponsiveness (AHR) and inflammation leading to airway remodeling (AR). In children, AR may occur very early prior to the age of 6 years. Treatments to prevent or reverse AR are unknown. AIM: We sought to determine (i) whether short allergenic sensitization at a young age in a mouse model may induce enhanced AR and inflammation compared to adults; (ii) the effect of Montelukast on such AR. METHODS: Immature and adult Balb/c mice were sensitized and challenged with ovalbumin...
June 2018: Pediatric Pulmonology
https://www.readbyqxmd.com/read/28984468/tgf-%C3%AE-1-evokes-human-airway-smooth-muscle-cell-shortening-and-hyperresponsiveness-via-smad3
#3
Christie A Ojiaku, Gaoyuan Cao, Wanqu Zhu, Edwin J Yoo, Maya Shumyatcher, Blanca E Himes, Steven S An, Reynold A Panettieri
Transforming growth factor β1 (TGF-β1), a cytokine whose levels are elevated in the airways of patients with asthma, perpetuates airway inflammation and modulates airway structural cell remodeling. However, the role of TGF-β1 in excessive airway narrowing in asthma, or airway hyperresponsiveness (AHR), remains unclear. In this study, we set out to investigate the direct effects of TGF-β1 on human airway smooth muscle (HASM) cell shortening and hyperresponsiveness. The dynamics of AHR and single-cell excitation-contraction coupling were measured in human precision-cut lung slices and in isolated HASM cells using supravital microscopy and magnetic twisting cytometry, respectively...
May 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28889952/orosomucoid-like-3-ormdl3-upregulates-airway-smooth-muscle-proliferation-contraction-and-ca-2-oscillations-in-asthma
#4
Jun Chen, Marina Miller, Hirotoshi Unno, Peter Rosenthal, Michael J Sanderson, David H Broide
BACKGROUND: Airway hyperresponsiveness is a major feature of asthma attributed predominantly to an extrinsic immune/inflammatory response increasing airway smooth muscle (ASM) contractility. OBJECTIVE: We investigated whether increased ASM expression of orosomucoid-like 3 (ORMDL3), a gene on chromosome 17q21 highly linked to asthma, induced increased ASM proliferation and contractility in vitro and influenced airway contractility and calcium flux in ASM in precision-cut lung slices (PCLSs) from wild-type and hORMDL3Zp3-Cre mice (which express increased levels of human ORMDL3 [hORMDL3])...
July 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28865134/human-pulmonary-3d-models-for-translational-research
#5
REVIEW
Katja Zscheppang, Johanna Berg, Sarah Hedtrich, Leonie Verheyen, Darcy E Wagner, Norbert Suttorp, Stefan Hippenstiel, Andreas C Hocke
Lung diseases belong to the major causes of death worldwide. Recent innovative methodological developments now allow more and more for the use of primary human tissue and cells to model such diseases. In this regard, the review covers bronchial air-liquid interface cultures, precision cut lung slices as well as ex vivo cultures of explanted peripheral lung tissue and de-/re-cellularization models. Diseases such as asthma or infections are discussed and an outlook on further areas for development is given. Overall, the progress in ex vivo modeling by using primary human material could make translational research activities more efficient by simultaneously fostering the mechanistic understanding of human lung diseases while reducing animal usage in biomedical research...
January 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/28323055/a-6-alkylsalicylate-histone-acetyltransferase-inhibitor-inhibits-histone-acetylation-and-pro-inflammatory-gene-expression-in-murine-precision-cut-lung-slices
#6
Thea van den Bosch, Niek G J Leus, Hannah Wapenaar, Alexander Boichenko, Jos Hermans, Rainer Bischoff, Hidde J Haisma, Frank J Dekker
Lysine acetylations are post-translational modifications of cellular proteins, that are crucial in the regulation of many cellular processes. Lysine acetylations on histone proteins are part of the epigenetic code regulating gene expression and are installed by histone acetyltransferases. Observations that inflammatory lung diseases, such as asthma and chronic obstructive pulmonary disease, are characterized by increased histone acetyltransferase activity indicate that development of small molecule inhibitors for these enzymes might be a valuable approach towards new therapies for these diseases...
June 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28278518/the-actin-regulator-zyxin-reinforces-airway-smooth-muscle-and-accumulates-in-airways-of-fatal-asthmatics
#7
MULTICENTER STUDY
Sonia R Rosner, Christopher D Pascoe, Elizabeth Blankman, Christopher C Jensen, Ramaswamy Krishnan, Alan L James, John G Elliot, Francis H Green, Jeffrey C Liu, Chun Y Seow, Jin-Ah Park, Mary C Beckerle, Peter D Paré, Jeffrey J Fredberg, Mark A Smith
Bronchospasm induced in non-asthmatic human subjects can be easily reversed by a deep inspiration (DI) whereas bronchospasm that occurs spontaneously in asthmatic subjects cannot. This physiological effect of a DI has been attributed to the manner in which a DI causes airway smooth muscle (ASM) cells to stretch, but underlying molecular mechanisms-and their failure in asthma-remain obscure. Using cells and tissues from wild type and zyxin-/- mice we report responses to a transient stretch of physiologic magnitude and duration...
2017: PloS One
https://www.readbyqxmd.com/read/27833558/serelaxin-elicits-bronchodilation-and-enhances-%C3%AE-adrenoceptor-mediated-airway-relaxation
#8
Maggie Lam, Simon G Royce, Chantal Donovan, Maria Jelinic, Laura J Parry, Chrishan S Samuel, Jane E Bourke
Treatment with β-adrenoceptor agonists does not fully overcome the symptoms associated with severe asthma. Serelaxin elicits potent uterine and vascular relaxation via its cognate receptor, RXFP1, and nitric oxide (NO) signaling, and is being clinically evaluated for the treatment of acute heart failure. However, its direct bronchodilator efficacy has yet to be explored. Tracheal rings were prepared from male Sprague-Dawley rats (250-350 g) and tricolor guinea pigs, and precision cut lung slices (PCLSs) containing intrapulmonary airways were prepared from rats only...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27482635/airway-remodeling-and-hyperreactivity-in-a-model-of-bronchopulmonary-dysplasia-and-their-modulation-by-il-1-receptor-antagonist
#9
Simon G Royce, Marcel F Nold, Christine Bui, Chantal Donovan, Maggie Lam, Emma Lamanna, Ina Rudloff, Jane E Bourke, Claudia A Nold-Petry
Bronchopulmonary dysplasia (BPD) is a chronic disease of extreme prematurity that has serious long-term consequences including increased asthma risk. We earlier identified IL-1 receptor antagonist (IL-1Ra) as a potent inhibitor of murine BPD induced by combining perinatal inflammation (intraperitoneal LPS to pregnant dams) and exposure of pups to hyperoxia (fraction of inspired oxygen = 0.65). In this study, we determined whether airway remodeling and hyperresponsiveness similar to asthma are evident in this model, and whether IL-1Ra is protective...
December 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27417329/inhibition-of-spleen-tyrosine-kinase-attenuates-ige-mediated-airway-contraction-and-mediator-release-in-human-precision-cut-lung-slices
#10
Cynthia J Koziol-White, Yanlin Jia, Gretchen A Baltus, Philip R Cooper, Dennis M Zaller, Michael A Crackower, Erich E Sirkowski, Steven Smock, Alan B Northrup, Blanca E Himes, Stephen E Alves, Reynold A Panettieri
BACKGROUND AND PURPOSE: Asthma presents as a heterogeneous syndrome characterized by airway obstruction, inflammation and hyper-reactivity (AHR). Spleen tyrosine kinase (Syk) mediates allergen-induced mast cell degranulation, a central component of allergen-induced inflammation and AHR. However, the role of Syk in IgE-mediated constriction of human small airways remains unknown. In this study, we addressed whether selective inhibition of Syk attenuates IgE-mediated constriction and mast cell mediator release in human small airways...
November 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27396568/store-operated-calcium-entry-is-required-for-sustained-contraction-and-ca-2-oscillations-of-airway-smooth-muscle
#11
Jun Chen, Michael J Sanderson
KEY POINTS: Airway hyper-responsiveness in asthma is driven by excessive contraction of airway smooth muscle cells (ASMCs). Agonist-induced Ca2+ oscillations underlie this contraction of ASMCs and the magnitude of this contraction is proportional to the Ca2+ oscillation frequency. Sustained contraction and Ca2+ oscillations require an influx of extracellular Ca2+ , although the mechanisms and pathways mediating this Ca2+ influx during agonist-induced ASMC contraction are not well defined...
May 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/27352269/inhibition-of-pi3k-promotes-dilation-of-human-small-airways-in-a-rho-kinase-dependent-manner
#12
Cynthia J Koziol-White, Edwin J Yoo, Gaoyuan Cao, Jie Zhang, Eleni Papanikolaou, Ivan Pushkarsky, Adam Andrews, Blanca E Himes, Robert D Damoiseaux, Stephen B Liggett, Dino Di Carlo, Richard C Kurten, Reynold A Panettieri
BACKGROUND AND PURPOSE: Asthma manifests as a heterogeneous syndrome characterized by airway obstruction, inflammation and hyperresponsiveness (AHR). Although the molecular mechanisms remain unclear, activation of specific PI3K isoforms mediate inflammation and AHR. We aimed to determine whether inhibition of PI3Kδ evokes dilation of airways and to elucidate potential mechanisms. EXPERIMENTAL APPROACH: Human precision cut lung slices from non-asthma donors and primary human airway smooth muscle (HASM) cells from both non-asthma and asthma donors were utilized...
September 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27149505/formaldehyde-induces-rho-associated-kinase-activity-to-evoke-airway-hyperresponsiveness
#13
Joseph Jude, Cynthia Koziol-White, Jacqueline Scala, Edwin Yoo, William Jester, Christopher Maute, Pamela Dalton, Reynold Panettieri
Formaldehyde, a common indoor air pollutant, exacerbates asthma and synergizes with allergen to induce airway hyperresponsiveness (AHR) in animal models. The mechanisms mediating formaldehyde-induced AHR remain poorly understood. We posit that formaldehyde modulates agonist-induced contractile response of human airway smooth muscle (HASM) cells to elicit AHR. HASM cells were exposed to formaldehyde or vehicle and agonist-induced intracellular Ca(2+) ([Ca(2+)]i) and myosin light-chain phosphatase (MYPT1) phosphorylation were determined...
October 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27128804/smoke-and-viruses-a-hindrance-to-relaxing-the-airways
#14
COMMENT
Aran Singanayagam, Sebastian L Johnston
Inhaled β2-adrenoceptor agonists are a mainstay of therapy for airways diseases and are almost universally prescribed for patients with asthma or chronic obstructive pulmonary disease (COPD). Very few studies have evaluated the efficacy of these commonly used therapies during acute disease exacerbations which are frequently triggered by viral infection. In this edition of Clinical Science, Donovan et al. assess the ex vivo effects of the most commonly used short-acting β2-agonist salbutamol on small airway reactivity using precision cut lung slices (PCLS) from a mouse model of virus-induced exacerbation of COPD...
May 1, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27128803/influenza-a-virus-infection-and-cigarette-smoke-impair-bronchodilator-responsiveness-to-%C3%AE-adrenoceptor-agonists-in-mouse-lung
#15
Chantal Donovan, Huei Jiunn Seow, Jane E Bourke, Ross Vlahos
β2-adrenoceptor agonists are the mainstay therapy for patients with asthma but their effectiveness in cigarette smoke (CS)-induced lung disease such as chronic obstructive pulmonary disease (COPD) is limited. In addition, bronchodilator efficacy of β2-adrenoceptor agonists is decreased during acute exacerbations of COPD (AECOPD), caused by respiratory viruses including influenza A. Therefore, the aim of the present study was to assess the effects of the β2-adrenoceptor agonist salbutamol (SALB) on small airway reactivity using mouse precision cut lung slices (PCLS) prepared from CS-exposed mice and from CS-exposed mice treated with influenza A virus (Mem71, H3N1)...
May 1, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/26718586/the-histone-acetyltransferase-p300-inhibitor-c646-reduces-pro-inflammatory-gene-expression-and-inhibits-histone-deacetylases
#16
Thea van den Bosch, Alexander Boichenko, Niek G J Leus, Maria E Ourailidou, Hannah Wapenaar, Dante Rotili, Antonello Mai, Axel Imhof, Rainer Bischoff, Hidde J Haisma, Frank J Dekker
Lysine acetylations are reversible posttranslational modifications of histone and non-histone proteins that play important regulatory roles in signal transduction cascades and gene expression. Lysine acetylations are regulated by histone acetyltransferases as writers and histone deacetylases as erasers. Because of their role in signal transduction cascades, these enzymes are important players in inflammation. Therefore, histone acetyltransferase inhibitors could reduce inflammatory responses. Among the few histone acetyltransferase inhibitors described, C646 is one of the most potent (Ki of 0...
February 15, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/26488271/cystic-fibrosis-transmembrane-conductance-regulator-in-sarcoplasmic-reticulum-of-airway-smooth-muscle-implications-for-airway-contractility
#17
Daniel P Cook, Michael V Rector, Drake C Bouzek, Andrew S Michalski, Nicholas D Gansemer, Leah R Reznikov, Xiaopeng Li, Mallory R Stroik, Lynda S Ostedgaard, Mahmoud H Abou Alaiwa, Michael A Thompson, Y S Prakash, Ramaswamy Krishnan, David K Meyerholz, Chun Y Seow, David A Stoltz
RATIONALE: An asthma-like airway phenotype has been described in people with cystic fibrosis (CF). Whether these findings are directly caused by loss of CF transmembrane conductance regulator (CFTR) function or secondary to chronic airway infection and/or inflammation has been difficult to determine. OBJECTIVES: Airway contractility is primarily determined by airway smooth muscle. We tested the hypothesis that CFTR is expressed in airway smooth muscle and directly affects airway smooth muscle contractility...
February 15, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/26386117/rosiglitazone-elicits-in-vitro-relaxation-in-airways-and-precision-cut-lung-slices-from-a-mouse-model-of-chronic-allergic-airways-disease
#18
Chantal Donovan, Simon R Bailey, Jenny Tran, Gertruud Haitsma, Zaridatul A Ibrahim, Simon R Foster, Mimi L K Tang, Simon G Royce, Jane E Bourke
Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor-γ (PPARγ) ligand, is a novel dilator of small airways in mouse precision cut lung slices (PCLS). In this study, relaxation to RGZ and β-adrenoceptor agonists were compared in trachea from naïve mice and guinea pigs and trachea and PCLS from a mouse model of chronic allergic airways disease (AAD). Airways were precontracted with methacholine before addition of PPARγ ligands [RGZ, ciglitazone (CGZ), or 15-deoxy-(Δ12,14)-prostaglandin J2 (15-deoxy-PGJ2)] or β-adrenoceptor agonists (isoprenaline and salbutamol)...
November 15, 2015: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/25874477/ryanodine-receptor-sensitization-results-in-abnormal-calcium-signaling-in-airway-smooth-muscle-cells
#19
Huguette Croisier, Xiahui Tan, Jun Chen, James Sneyd, Michael J Sanderson, Bindi S Brook
Intracellular Ca(2+) dynamics of airway smooth muscle cells (ASMCs) are believed to play a major role in airway hyperresponsiveness and remodeling in asthma. Prior studies have underscored a prominent role for inositol 1,4,5-triphosphate (IP3) receptors in normal agonist-induced Ca(2+) oscillations, whereas ryanodine receptors (RyRs) appear to remain closed during such Ca(2+) oscillations, which mediate ASMC contraction. Nevertheless, RyRs have been hypothesized to play a role in hyperresponsive Ca(2+) signaling...
November 2015: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/25605999/airway-smooth-muscle-sensitivity-to-methacholine-in-precision-cut-lung-slices-pcls-from-ovalbumin-induced-asthmatic-mice
#20
Hae Jin Kim, Yeryung Kim, Su Jung Park, Boram Bae, Hye-Ryun Kang, Sang-Heon Cho, Hae Young Yoo, Joo Hyun Nam, Woo Kyung Kim, Sung Joon Kim
Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR) and reversible airway obstruction. Methacholine (MCh) is widely used in broncho-provocation test to evaluate airway resistance. For experimental investigation, ovalbumin-induced sensitization is frequently used in rodents (Ova-asthma). However, albeit the inflammatory histology and AHR in vivo, it remains unclear whether the MCh sensitivity of airway smooth muscle isolated from Ova-asthma is persistently changed. In this study, the contractions of airways in precision-cut lung slices (PCLS) from control, Ova-asthma, and IL-13 overexpressed transgenic mice (IL-13TG) were compared by analyzing the airway lumen space (AW)...
January 2015: Korean Journal of Physiology & Pharmacology
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