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https://www.readbyqxmd.com/read/28108847/airway-mucus-inflammation-and-remodeling-emerging-links-in-the-pathogenesis-of-chronic-lung-diseases
#1
REVIEW
Zhe Zhou-Suckow, Julia Duerr, Matthias Hagner, Raman Agrawal, Marcus A Mall
Airway mucus obstruction is a hallmark of many chronic lung diseases including rare genetic disorders such as cystic fibrosis (CF) and primary ciliary dyskinesia, as well as common lung diseases such as asthma and chronic obstructive pulmonary disease (COPD), which have emerged as a leading cause of morbidity and mortality worldwide. However, the role of excess airway mucus in the in vivo pathogenesis of these diseases remains poorly understood. The generation of mice with airway-specific overexpression of epithelial Na(+) channels (ENaC), exhibiting airway surface dehydration (mucus hyperconcentration), impaired mucociliary clearance (MCC) and mucus plugging, led to a model of muco-obstructive lung disease that shares key features of CF and COPD...
January 20, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28108561/semaphorin-3e-deficiency-exacerbates-airway-inflammation-hyperresponsiveness-and-remodeling-in-a-mouse-model-of-allergic-asthma
#2
Hesam Movassagh, Lianyu Shan, Ashfaque Mohammed, Andrew J Halayko, Abdelilah S Gounni
Semaphorin 3E (Sema3E) plays a crucial role in axon guidance, vascular patterning, and immune regulation. Nevertheless, the role of Sema3E in asthma is still elusive. In this study, we show that genetic ablation of Sema3E in mice results in increased lung granulocytosis, airway hyperresponsiveness, mucus overproduction, collagen deposition, and Th2/Th17 inflammation. Transfer of Sema3e(-/-) bone marrow progenitor cells to irradiated wild-type (WT) recipients exacerbates airway hyperresponsiveness and inflammation, whereas transfer of WT bone marrow progenitor cells ameliorates asthma pathology in Sema3e(-/-) recipients...
January 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28107494/protective-roles-for-rgs2-in-a-mouse-model-of-house-dust-mite-induced-airway-inflammation
#3
Tresa George, Matthew Bell, Mainak Chakraborty, David P Siderovski, Mark A Giembycz, Robert Newton
The GTPase-accelerating protein, regulator of G-protein signalling 2 (RGS2) reduces signalling from G-protein-coupled receptors (GPCRs) that signal via Gαq. In humans, RGS2 expression is up-regulated by inhaled corticosteroids (ICSs) and long-acting β2-adrenoceptor agonists (LABAs) such that synergy is produced in combination. This may contribute to the superior clinical efficacy of ICS/LABA therapy in asthma relative to ICS alone. In a murine model of house dust mite (HDM)-induced airways inflammation, three weeks of intranasal HDM (25 μg, 3×/week) reduced lung function and induced granulocytic airways inflammation...
2017: PloS One
https://www.readbyqxmd.com/read/28102546/ataluren-and-similar-compounds-specific-therapies-for-premature-termination-codon-class-i-mutations-for-cystic-fibrosis
#4
REVIEW
Aisha A Aslam, Colin Higgins, Ian P Sinha, Kevin W Southern
BACKGROUND: Cystic fibrosis is a common life-shortening genetic disorder in the Caucasian population (less common in other ethnic groups) caused by the mutation of a single gene that codes for the production of the cystic fibrosis transmembrane conductance regulator protein. This protein coordinates the transport of salt (and bicarbonate) across cell surfaces and the mutation most notably affects the airways. In the lungs of people with cystic fibrosis, defective protein results in a dehydrated surface liquid and compromised mucociliary clearance...
January 19, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28093718/ribosomal-protein-s3-gene-silencing-protects-against-experimental-allergic-asthma
#5
Jinrui Dong, Wupeng Liao, Hong Yong Peh, Tze Khee Chan, W S Daniel Tan, Li Li, Amy Yong, W S Fred Wong
BACKGROUND AND PURPOSE: Ribosomal protein S3 (RPS3) is a 40S ribosomal protein of the S3P family essential for executing protein translation. RPS3 has recently been found to interact with the p65 subunit of the NF-κB complex, and promote p65 DNA-binding activity. Persistent activation of the NF-κB pathway is evident in allergic asthma. We hypothesized that gene silencing of lung RPS3 can ameliorate allergic airway inflammation. EXPERIMENTAL APPROACH: Gene silencing efficacy of RPS3 siRNA was screened in three different mouse cell lines by real-time PCR and immunoblotting...
January 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28077104/effects-of-treadmill-exercise-versus-flutter%C3%A2-on-respiratory-flow-and-sputum-properties-in-adults-with-cystic-fibrosis-a-randomised-controlled-cross-over-trial
#6
Tiffany J Dwyer, Rahizan Zainuldin, Evangelia Daviskas, Peter T P Bye, Jennifer A Alison
BACKGROUND: Treadmill exercise and airway clearance with the Flutter® device have previously been shown to improve mucus clearance mechanisms in people with cystic fibrosis (CF) but have not been compared. It is therefore not known if treadmill exercise is an adequate form of airway clearance that could replace established airway clearance techniques, such as the Flutter®. The aim of this study was to evaluate respiratory flow, sputum properties and subjective responses of treadmill exercise and Flutter® therapy, compared to resting breathing (control)...
January 11, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28075489/cough-augmentation-techniques-for-extubation-or-weaning-critically-ill-patients-from-mechanical-ventilation
#7
REVIEW
Louise Rose, Neill Kj Adhikari, David Leasa, Dean A Fergusson, Douglas McKim
BACKGROUND: There are various reasons why weaning and extubation failure occur, but ineffective cough and secretion retention can play a significant role. Cough augmentation techniques, such as lung volume recruitment or manually- and mechanically-assisted cough, are used to prevent and manage respiratory complications associated with chronic conditions, particularly neuromuscular disease, and may improve short- and long-term outcomes for people with acute respiratory failure. However, the role of cough augmentation to facilitate extubation and prevent post-extubation respiratory failure is unclear...
January 11, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28068894/strain-differences-in-a-murine-model-of-air-pollutant-induced-nonatopic-asthma-and-rhinitis
#8
Jack R Harkema, Lucas A Hotchkiss, Nicholas A Vetter, Daven N Jackson-Humbles, Ryan P Lewandowski, James G Wagner
Ozone is an irritating gas found in photochemical smog. Epidemiological associations have been made between the onset of asthma and childhood exposures to increasing levels of ambient ozone (i.e., air pollutant-induced nonatopic asthma). Individuals, however, vary in their susceptibility to this outdoor air pollutant, which may be due, in part, to their genetic makeup. The present study was designed to test the hypothesis that there are murine strain-dependent differences in pulmonary and nasal pathologic responses to repeated ozone exposures...
January 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28062483/the-sialic-acid-to-urea-ratio-as-a-measure-of-airway-surface-hydration
#9
Charles R Esther, David B Hill, Brian Button, Shuai Shi, Corey M Jania, Elizabeth A Duncan, Claire M Doerschuk, Gang Chen, Sarath Ranganathan, Stephen Michael Stick, Richard C Boucher
INTRODUCTION: Although airway mucus dehydration is key to pathophysiology of cystic fibrosis (CF) and other airways diseases, measuring mucus hydration is challenging. We explored a robust method to estimate mucus hydration using sialic acid as a marker for mucin content. METHODS: Terminal sialic acid residues from mucins were cleaved by acid hydrolysis from airway samples, and concentrations of sialic acid, urea, and other biomarkers analyzed using mass spectrometry...
January 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28052955/hypoxia-and-sterile-inflammation-in-cystic-fibrosis-airways-mechanisms-and-potential-therapies
#10
REVIEW
Samuel T Montgomery, Marcus A Mall, Anthony Kicic, Stephen M Stick
Cystic fibrosis is one of the most common autosomal recessive genetic diseases in Caucasian populations. Diagnosis via newborn screening and targeted nutritional and antibiotic therapy have improved outcomes, however respiratory failure remains the key cause of morbidity and mortality. Progressive respiratory disease in cystic fibrosis is characterised by chronic neutrophilic airway inflammation associated with structural airway damage leading to bronchiectasis and decreased lung function. Mucus obstruction is a characteristic early abnormality in the cystic fibrosis airway, associated with neutrophilic inflammation often in the absence of detectable infection...
January 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28045493/inhalation-and-oropharyngeal-aspiration-exposure-to-rod-like-carbon-nanotubes-induce-similar-airway-inflammation-and-biological-responses-in-mouse-lungs
#11
Pia Kinaret, Marit Ilves, Vittorio Fortino, Elina Rydman, Piia Karisola, Anna Lähde, Joonas Koivisto, Jorma Jokiniemi, Henrik Wolff, Kai Savolainen, Dario Greco, Harri Alenius
Carbon nanotubes (CNT) have the potential to great impact on technological and industrial progress, but their production and use may, in some cases, cause serious health problems. Certain rod-shaped multi-walled CNT (rCNT) can, in fact, induce severe asbestos-like pathogenicity in mice, including granuloma formation, fibrosis and even cancer. Evaluating the comparability between alternative hazard assessment methods is needed to ensure fast and reliable evaluation of the potentially adverse effects of these materials...
January 3, 2017: ACS Nano
https://www.readbyqxmd.com/read/28035597/identification-of-essential-genes-of-pseudomonas-aeruginosa-for-its-growth-in-airway-mucus
#12
Mohammed Abd Alrahman, Sang Sun Yoon
Pseudomonas aeruginosa has been identified as an important causative agent of airway infection, mainly in cystic fibrosis. This disease is characterized by defective mucociliary clearance induced in part by mucus hyper-production. Mucin is a major component of airway mucus and is heavily O-glycosylated, with a protein backbone. Airway infection is known to be established with bacterial adhesion to mucin. However, the genes involved in mucin degradation or utilization remain elusive. In this study, we sought to provide a genetic basis of P...
January 2017: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/28035388/the-effect-of-inhaled-inactived-mycobacterium%C3%A2-phlei-as-a-treatment-for-asthma
#13
Moyu Ming, Chaoqian Li, Zhixi Luo, Shengqiu Lv, Qixiang Sun
Allergic asthma is a chronic airway disorder characterized by airway inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR). A murine model of asthma was used to examine the antiasthmatic effect of inhaled inactived Mycobacterium phlei (M. phlei). AHR, neutrophil levels, eosinophil levels and levels of interleukin (IL)‑17 and IL‑23 receptor (IL‑23R) were monitored. The results demonstrated that inactivated M. phlei alleviates the IL‑17+γδT cell‑mediated immune response and attenuates airway inflammation and airway hyperresponsiveness in the asthmatic murine lung, partially through inhibiting the expression of IL‑23R...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28030368/sphingolipids-ormdl3-and-asthma-what-is-the-evidence
#14
Tilla S Worgall
PURPOSE OF REVIEW: Genome-wide association studies identified ORMDL3, a protein of the endoplasmic reticulum, as a significant asthma risk factor. ORMDL3 is one of three ORMDL proteins that integrate multiple signals to maintain sphingolipid homeostasis. Studies that investigated potential mechanisms for how increased ORMDL3 might affect asthma are summarized. RECENT FINDINGS: Investigations focused on decreased sphingolipid synthesis and on the unfolded protein response because ORMDL3 had been implicated in both...
December 24, 2016: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28025644/tnf%C3%AE-affects-ciliary-beat-response-to-increased-viscosity-in-human-pediatric-airway-epithelium
#15
Claudia González, Karla Droguett, Mariana Rios, Noam A Cohen, Manuel Villalón
In airway epithelium, mucociliary clearance (MCC) velocity depends on the ciliary beat frequency (CBF), and it is affected by mucus viscoelastic properties. Local inflammation induces secretion of cytokines (TNFα) that can alter mucus viscosity; however airway ciliated cells have an autoregulatory mechanism to prevent the collapse of CBF in response to increase in mucus viscosity, mechanism that is associated with an increment in intracellular Ca(+2) level ([Ca(2+)]i). We studied the effect of TNFα on the autoregulatory mechanism that regulates CBF in response to increased viscosity using dextran solutions, in ciliated cells cultured from human pediatric epithelial adenoid tissue...
2016: BioMed Research International
https://www.readbyqxmd.com/read/28024734/lyn-kinase-represses-mucus-hypersecretion-by-regulating-il-13-induced-endoplasmic-reticulum-stress-in-asthma
#16
Xing Wang, Xiaoqiong Yang, Yin Li, Xiaoyun Wang, Yun Zhang, Xi Dai, Bin Niu, Juan Wu, Xiefang Yuan, Anjie Xiong, Zhigang Liu, Nanshan Zhong, Min Wu, Guoping Li
In asthma, mucus hypersecretion is thought to be a prominent pathological feature associated with widespread mucus plugging. However, the current treatments for mucus hypersecretion are often ineffective or temporary. The potential therapeutic targets of mucus hypersecretion in asthma remain unknown. Here, we show that Lyn is a central effector of endoplasmic reticulum stress (ER stress) and mucous hypersecretion in asthma. In Lyn-transgenic mice (Lyn-TG) and wild-type (WT) C57BL/6J mice exposed to ovalbumin (OVA), Lyn overexpression attenuates mucus hypersecretion and ER stress...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28011616/targeted-epigenetic-editing-of-spdef-reduces-mucus-production-in-lung-epithelial-cells
#17
Juan Song, David Cano Rodriguez, Melanie Winkle, Rutger A F Gjaltema, Désirée Goubert, Tomasz P Jurkowski, Irene H Heijink, Marianne G Rots, Machteld N Hylkema
Airway mucus hypersecretion contributes to the morbidity and mortality in patients with chronic inflammatory lung diseases. Reducing mucus production is crucial for improving patients' quality of life. The transcription factor SAM-pointed domain-containing Ets-like factor (SPDEF) plays a critical role in the regulation of mucus production, and therefore represents a potential therapeutic target. This study aims to reduce lung epithelial mucus production by targeted silencing SPDEF using the novel strategy epigenetic editing...
December 23, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28006108/preliminary-assessment-of-safety-pharmacokinetics-and-dose-finding-for-digitoxin-for-airway-inflammation-in-cystic-fibrosis
#18
Pamela L Zeitlin, Marie Diener-West, Karen A Callahan, Seakwoo Lee, C Conover Talbot, Bette Pollard, Michael P Boyle, Noah Lechtzin
RATIONALE: Cystic Fibrosis (CF) lung disease progresses by a combination of airways inflammation, bacterial colonization, and infection. Airways inflammation is predominantly neutrophilic and complicates airway clearance therapies through cellular debris, excessive DNA, excessive and viscous mucous, and high concentrations of neutrophils, Il-8 and related cytokines liberated along the NFkB signaling pathway. OBJECTIVE: We conducted a single site, randomized, double blind, placebo-controlled, preliminary study in which we evaluated the effects of 28 days of two dose levels (0...
December 22, 2016: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/27995616/b-cell-subsets-are-modulated-during-allergic-airway-inflammation-but-are-not-required-for-the-development-of-respiratory-tolerance-in-a-murine-model
#19
Anika Habener, Ann-Kathrin Behrendt, Jelena Skuljec, Adan Chari Jirmo, Almut Meyer-Bahlburg, Gesine Hansen
Allergic asthma is a widespread chronic inflammatory disease of the airways. The role of different B-cell subsets in developing asthma and respiratory tolerance is not well-known. Especially regulatory B (Breg) cells are proposed to be important in asthma regulation. Using wildtype (WT) and B-cell-deficient (μMT) mice we investigated how B-cells are affected by induction of allergic airway inflammation and respiratory tolerance and whether they are necessary to develop these conditions. WT mice with an asthma-like phenotype, characterized by increased airway hyperreactivity, eosinophilic airway inflammation, mucus hypersecretion and elevated Th2 cytokines, exhibited increased MHCII and CD23 expression on follicular mature B-cells in lung, bronchial lymph nodes (bLN) and spleen, which contributed to allergen-specific T-cell proliferation in vitro...
December 20, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27992060/cb2-receptors-regulate-natural-killer-cells-that-limit-allergic-airway-inflammation-in-a-murine-model-of-asthma
#20
M E Ferrini, S Hong, A Stierle, D Stierle, N Stella, K Roberts, Z Jaffar
BACKGROUND: Allergic asthma is a chronic airway inflammatory disease involving the complementary actions of innate and adaptive immune responses. Endogenously generated cannabinoids, acting via CB2 receptors play important roles in both homeostatic and inflammatory processes. However, the contribution of CB2-acting eicosanoids to the innate events preceding sensitization to the common house dust mite (HDM) allergen, remain to be elucidated. We investigated the role of CB2 activation during allergen-induced pulmonary inflammation and NK cell effector function...
December 19, 2016: Allergy
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