Read by QxMD icon Read

Precision cut lung slice, asthma

Julia Herbert, Horst Thiermann, Franz Worek, Timo Wille
CONTEXT: Nerve agents like sarin or VX have repeatedly been used in military conflicts or homicidal attacks, as seen in Syria or Malaysia 2017. Together with pesticides, nerve agents assort as organophosphorus compounds (OP), which inhibit the enzyme acetylcholinesterase. To counteract subsequent fatal symptoms due to acetylcholine (ACh) accumulation, oximes plus atropine are administered, a regimen that lacks efficacy in several cases of OP poisoning. New therapeutics are in development, but still need evaluation before clinical employment...
January 30, 2019: Clinical Toxicology
Olga Danov, Sharon Melissa Jiménez Delgado, Helena Obernolte, Sophie Seehase, Susann Dehmel, Peter Braubach, Hans-Gerd Fieguth, Gabriele Matschiner, Mary Fitzgerald, Danny Jonigk, Sascha Knauf, Olaf Pfennig, Gregor Warnecke, Judy Wichmann, Armin Braun, Katherina Sewald
Subgroups of patients with severe asthma are insensitive to inhaled corticosteroids and require novel therapies on top of standard medical care. IL-13 is considered one of the key cytokines in the asthma pathogenesis, however, the effect of IL-13 was mostly studied in rodents. This study aimed to assess IL-13 effect in human lung tissue for the development of targeted therapy approaches such as inhibition of soluble IL-13 or its receptor IL-4Rα subunit. Precision-cut lung slices (PCLS) were prepared from lungs of rodents, non-human primates (NHP) and humans...
2018: PloS One
Gene T Yocum, Jose F Perez-Zoghbi, Jennifer Danielsson, Aisha S Kuforiji, Yi Zhang, Guanguan Li, M S Rashid Roni, Revathi Kodali, Douglas C Stafford, Leggy A Arnold, James M Cook, Charles W Emala
Airway smooth muscle cells express GABAA receptors, and previous reports have demonstrated that GABAA receptor activators relax airway smooth muscle. However, given the activity of GABAA receptors in central nervous system inhibitory neurotransmission, concern exists that these activators may lead to undesirable sedation. MIDD0301 is a novel imidazobenzodiazepine and positive allosteric modulator of the GABAA receptor with limited brain distribution, thus eliminating the potential for sedation. Here we demonstrate that MIDD0301 relaxes histamine-contracted guinea pig (p<0...
November 29, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Joshua L Kennedy, Richard C Kurten, Sandra McCullough, Reynold A Panettieri, Cynthia Koziol-White, Stacie M Jones, Katherine Caid, Pritmohinder S Gill, Dean Roberts, Hartmut Jaeschke, Mitchell R McGill, Laura James
INTRODUCTION: Epidemiologic studies have demonstrated an association between acetaminophen (APAP) use and the development of asthma symptoms. However, few studies have examined relationships between APAP-induced signaling pathways associated with the development of asthma symptoms. We tested the hypothesis that acute APAP exposure causes airway hyper-responsiveness (AHR) in human airways. METHODS: Precision cut lung slice (PCLS) airways from humans and mice were used to determine the effects of APAP on airway bronchoconstriction and bronchodilation and to assess APAP metabolism in lungs...
October 17, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
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
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
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
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
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
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
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
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
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
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
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
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
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 Ca2+ ([Ca2+ ]i ) and myosin light-chain phosphatase (MYPT1) phosphorylation were determined...
October 2016: American Journal of Respiratory Cell and Molecular Biology
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-)
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-)
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
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"