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Mechanism secretion of airways mucus

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https://www.readbyqxmd.com/read/28566470/early-life-allergen-induced-mucus-overproduction-requires-augmented-neural-stimulation-of-pulmonary-neuroendocrine-cell-secretion
#1
Juliana Barrios, Kruti R Patel, Linh Aven, Rebecca Achey, Martin S Minns, Yoonjoo Lee, Vickery E Trinkaus-Randall, Xingbin Ai
Pulmonary neuroendocrine cells (PNECs) are the only innervated airway epithelial cells. To what extent neural innervation regulates PNEC secretion and function is unknown. Here, we discover that neurotrophin 4 (NT4) plays an essential role in mucus overproduction after early life allergen exposure by orchestrating PNEC innervation and secretion of GABA. We found that PNECs were the only cellular source of GABA in airways. In addition, PNECs expressed NT4 as a target-derived mechanism underlying PNEC innervation during development...
May 31, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28546154/synergistic-mucus-secretion-by-histamine-and-il-4-through-tmem16a-in-airway-epithelium
#2
Ju Wan Kang, Yong Hyuk Lee, Min Jeong Kang, Hyun Jae Lee, Ryung Oh, Hyun Jin Min, Wan Namkung, Jae Young Choi, Sang Nam Lee, Chang-Hoon Kim, Joo-Heon Yoon, Hyung-Ju Cho
Histamine is an important mediator of allergic reactions, and mucus hypersecretion is a major allergic symptom. However, the direct effect of histamine on mucus secretion from airway mucosal epithelia has not been clearly demonstrated. TMEM16A is a Ca2+-activated chloride channel, and it is closely related to fluid secretion in airway mucosal epithelia. We investigated whether histamine directly induces fluid secretion from epithelial cells or submucosal glands (SMG) and mechanisms related therewith in allergic airway diseases...
May 25, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28476309/bombesin-receptor-activated-protein-regulates-neutrophil-elastase-induced-mucin-5ac-hypersecretion-in-human-bronchial-epithelial-cells
#3
Qing Xu, Ling-Xiu Chen, Dan-Hua Ran, Wen-Yue Xie, Xiang-Dong Zhou
Bombesin receptor-activated protein (BRAP) is highly expressed in human bronchial epithelial cells. Recent studies have shown that BRAP reduces oxidative stress, inhibits airway inflammation and suppresses nuclear factor kappaB (NF-κB) activity. Mucus overproduction is an important feature in patients with chronic inflammatory airway diseases. Neutrophil elastase (NE) is a potent inducer of mucin5AC (MUC5AC), which is considered the predominant mucin secreted by human airway epithelial cells. Here, we hypothesize that BRAP may regulate NE-induced MUC5AC hypersecretion in a bronchial epithelial cell line (HBE16)...
May 2, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28397820/bitter-taste-receptor-agonists-mitigate-features-of-allergic-asthma-in-mice
#4
Pawan Sharma, Roslyn Yi, Ajay P Nayak, Nadan Wang, Francesca Tang, Morgan J Knight, Shi Pan, Brian Oliver, Deepak A Deshpande
Asthma is characterized by airway inflammation, mucus secretion, remodeling and hyperresponsiveness (AHR). Recent research has established the bronchodilatory effect of bitter taste receptor (TAS2R) agonists in various models. Comprehensive pre-clinical studies aimed at establishing effectiveness of TAS2R agonists in disease models are lacking. Here we aimed to determine the effect of TAS2R agonists on features of asthma. Further, we elucidated a mechanism by which TAS2R agonists mitigate features of asthma...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223396/personalising-airway-clearance-in-chronic-lung-disease
#5
REVIEW
Maggie McIlwaine, Judy Bradley, J Stuart Elborn, Fidelma Moran
This review describes a framework for providing a personalised approach to selecting the most appropriate airway clearance technique (ACT) for each patient. It is based on a synthesis of the physiological evidence that supports the modulation of ventilation and expiratory airflow as a means of assisting airway clearance. Possession of a strong understanding of the physiological basis for ACTs will enable clinicians to decide which ACT best aligns with the individual patient's pathology in diseases with anatomical bronchiectasis and mucus hypersecretion...
January 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28145442/elevated-gdf-15-contributes-to-pulmonary-inflammation-upon-cigarette-smoke-exposure
#6
F M Verhamme, L J M Seys, E G De Smet, S Provoost, W Janssens, D Elewaut, G F Joos, G G Brusselle, K R Bracke
The molecular mechanisms underlying the pathogenesis of chronic obstructive pulmonary disease (COPD) are still unclear, however signaling pathways associated with lung development, such as the transforming growth factor (TGF)-β superfamily, could be implicated in COPD. Growth differentiation factor (GDF)-15, a member of the TGF-β superfamily, is involved in inflammation, mucus secretion, and cachexia. We analyzed the pulmonary expression of GDF-15 in smokers and patients with COPD, in cigarette smoke (CS)-exposed cultures of primary human bronchial epithelial cells (pHBECs), and in CS-exposed mice...
February 1, 2017: Mucosal Immunology
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/28025644/tnf%C3%AE-affects-ciliary-beat-response-to-increased-viscosity-in-human-pediatric-airway-epithelium
#8
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/27977296/phosphoinositide-3-kinase-in-asthma-novel-roles-and-therapeutic-approaches
#9
Edwin J Yoo, Christie A Ojiaku, Krishna Sunder, Reynold A Panettieri
Asthma manifests as airway hyperresponsiveness and inflammation, including coughing, wheezing, and shortness of breath. Immune cells and airway structural cells orchestrate asthma pathophysiology, leading to mucus secretion, airway narrowing, and obstruction. Phosphoinositide 3-kinase (PI3K), a lipid kinase, plays a crucial role in many of the cellular and molecular mechanisms driving asthma pathophysiology, and represents an attractive therapeutic target. Here, we summarize the diverse roles of PI3K in the pathogenesis of asthma and discuss novel therapeutic approaches to treatment...
December 15, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27865862/impaired-mucus-clearance-exacerbates-allergen-induced-type-2-airway-inflammation-in-juvenile-mice
#10
Benedikt Fritzsching, Matthias Hagner, Lu Dai, Sandra Christochowitz, Raman Agrawal, Charlotte van Bodegom, Simone Schmidt, Jolanthe Schatterny, Stephanie Hirtz, Ryan Brown, Michelle Goritzka, Julia Duerr, Zhe Zhou-Suckow, Marcus A Mall
BACKGROUND: Type 2 airway inflammation plays a central role in the pathogenesis of allergen-induced asthma, but the underlying mechanisms remain poorly understood. Recently, we demonstrated that reduced mucociliary clearance, a characteristic feature of asthma, produces spontaneous type 2 airway inflammation in juvenile β-epithelial Na(+) channel (Scnn1b)-transgenic (Tg) mice. OBJECTIVE: We sought to determine the role of impaired mucus clearance in the pathogenesis of allergen-induced type 2 airway inflammation and identify cellular sources of the signature cytokine IL-13...
November 16, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27825045/therapeutic-effects-of-rosmarinic-acid-on-airway-responses-in-a-murine-model-of-asthma
#11
Zhengmin Liang, Haiying Nie, Yangfeng Xu, Jianbo Peng, Yun Zeng, Yingyi Wei, Xuemei Wen, Jiaming Qiu, Weiting Zhong, Xuming Deng, Jiakang He
Rosmarinic acid (RA) is an active component of a traditional Chinese herbal medicine. Previously, we reported that RA exerted a strong anti-inflammatory effect in a mouse acute lung injury model. Therefore, we hypothesized that RA might also have potential therapeutic effects in a murine model of asthma. In this study, we aimed to evaluate the anti-asthmatic activity of RA and explored its possible molecular mechanisms of action. Female BALB/c mice that had been sensitized to and challenged with ovalbumin (Ova) were treated with RA (20mg/kg) 1h after challenge...
December 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27799314/il-27-is-essential-for-suppression-of-experimental-allergic-asthma-by-the-tlr7-8-agonist-r848-resiquimod
#12
Adan Chari Jirmo, Kathleen Daluege, Christine Happle, Melanie Albrecht, Anna-Maria Dittrich, Mandy Busse, Anika Habener, Jelena Skuljec, Gesine Hansen
Different models of experimental allergic asthma have shown that the TLR7/8 agonist resiquimod (R848) is a potential inhibitor of type 2 helper cell-driven inflammatory responses. However, the mechanisms mediating its therapeutic effects are not fully understood. Using a model of experimental allergic asthma, we show that induction of IL-27 by R848 is critical for the observed ameliorative effects. R848 significantly inhibited all hallmarks of experimental allergic asthma, including airway hyperreactivity, eosinophilic airway inflammation, mucus hypersecretion, and Ag-specific Ig production...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27794589/tilianin-inhibits-muc5ac-expression-mediated-via-down-regulation-of-egfr-mek-erk-sp1-signaling-pathway-in-nci-h292-human-airway-cells
#13
Won-Yong Song, Yong-Seok Song, Hyung Won Ryu, Sei-Ryang Oh, JinTae Hong, Do-Young Yoon
In human airway, mucus exists to protect respiratory system as a primary barrier of innate immune system. However, hyper-expressed mucus limits airflow, resulting in decrease of lung function. Among more than 20 mucin family, MUC5AC and MUC5B are major glycoproteins in human airway mucus. Epidermal growth factor receptor (EGFR) signaling pathway is one of the mechanisms of these mucins expression and Specificity protein-1 (Sp1) transcription factor is the downstream signal of this pathway, playing pivotal roles in mucin expression...
October 28, 2016: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27637004/a-critical-evaluation-of-anti-il-13-and-anti-il-4-strategies-in-severe-asthma
#14
REVIEW
Diego Bagnasco, Matteo Ferrando, Gilda Varricchi, Giovanni Passalacqua, Giorgio Walter Canonica
Asthma is a high-prevalence disease, still accounting for mortality and high direct and indirect costs. It is now recognized that, despite the implementation of guidelines, a large proportion of cases remain not controlled. Certainly, adherence to therapy and the education of patients remain the primary objective, but the increasingly detailed knowledge about the pathogenic mechanisms and new biotechnologies offer the opportunity to better address and treat the disease. Interleukin (IL)-13 and IL-4 appear as the most suitable targets to treat the T helper 2 (TH2)-mediated forms (endotypes) of asthma...
2016: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/27625638/the-role-of-bacterial-secretion-systems-in-the-virulence-of-gram-negative-airway-pathogens-associated-with-cystic-fibrosis
#15
REVIEW
Sofie Depluverez, Simon Devos, Bart Devreese
Cystic fibrosis (CF) is the most common lethal inherited disorder in Caucasians. It is caused by mutation of the CF transmembrane conductance regulator (CFTR) gene. A defect in the CFTR ion channel causes a dramatic change in the composition of the airway surface fluid, leading to a highly viscous mucus layer. In healthy individuals, the majority of bacteria trapped in the mucus layer are removed and destroyed by mucociliary clearance. However, in the lungs of patients with CF, the mucociliary clearance is impaired due to dehydration of the airway surface fluid...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27624630/cough-augmentation-techniques-in-the-critically-ill-a-canadian-national-survey
#16
Louise Rose, Neill K Adhikari, Joseph Poon, David Leasa, Douglas A McKim
BACKGROUND: Critically ill mechanically ventilated patients experience impaired airway clearance due to ineffective cough and impaired secretion mobilization. Cough augmentation techniques, including mechanical insufflation-exsufflation (MI-E), manually assisted cough, and lung volume recruitment, improve cough efficiency. Our objective was to describe use, indications, contraindications, interfaces, settings, complications, and barriers to use across Canada. METHODS: An e-mail survey was sent to nominated local survey champions in eligible Canadian units (ICUs, weaning centers, and intermediate care units) with 4 telephone/e-mail reminders...
October 2016: Respiratory Care
https://www.readbyqxmd.com/read/27588910/interleukin-13-stimulates-muc5ac-expression-via-a-stat6-tmem16a-erk1-2-pathway-in-human-airway-epithelial-cells
#17
Yanling Qin, Youfan Jiang, Awais Shafiq Sheikh, Shanshan Shen, Jing Liu, Depeng Jiang
Transmembrane protein 16A (TMEM16A), a channel underlying the calcium-activated chloride channel (CaCC) currents, has been shown to be a key regulator of mucus overproduction in airway epithelial cells. However, the precise molecular mechanism involved in the TMEM16A-mediated mucus secretion remains unclear. In the present study, we inquired into a novel signaling mechanism for TMEM16A driving mucin 5AC (MUC5AC) production in human airway epithelial cells. Following treatment for 24-48h with type 13 interleukin (IL-13), an upregulation of TMEM16A expression in both mRNA and protein levels was observed in human bronchial epithelial cell line (HBE16), while signal transducer and activator of transcription 6 (STAT6) inhibition could decrease this elevated expression, suggesting that the regulation of TMEM16A expression by IL-13 was via a STAT6-based transcriptional mechanism...
November 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27535564/micropatterned-endotracheal-tubes-reduce-secretion-related-lumen-occlusion
#18
Ethan E Mann, Chelsea M Magin, M Ryan Mettetal, Rhea M May, MiKayla M Henry, Heather DeLoid, Justin Prater, Lauren Sullivan, John G Thomas, Mark D Twite, Albert E Parker, Anthony B Brennan, Shravanthi T Reddy
Tracheal intubation disrupts physiological homeostasis of secretion production and clearance, resulting in secretion accumulation within endotracheal tubes (ETTs). Novel in vitro and in vivo models were developed to specifically recapitulate the clinical manifestations of ETT occlusion. The novel Sharklet™ micropatterned ETT was evaluated, using these models, for the ability to reduce the accumulation of both bacterial biofilm and airway mucus compared to a standard care ETT. Novel ETTs with micropattern on the inner and outer surfaces were placed adjacent to standard care ETTs in in vitro biofilm and airway patency (AP) models...
December 2016: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/27477308/cold-inducible-rna-binding-protein-mediates-airway-inflammation-and-mucus-hypersecretion-through-a-post-transcriptional-regulatory-mechanism-under-cold-stress
#19
Yang Juan, Wu Haiqiao, Wenyao Xie, Huang Huaping, Han Zhong, Zhou Xiangdong, Victor P Kolosov, Juliy M Perelman
Acute or chronic cold exposure exacerbates chronic inflammatory airway diseases, such as chronic obstructive pulmonary disease (COPD) and asthma. Cold-inducible RNA-binding protein (CIRP) is a cold-shock protein and is induced by various environmental stressors, such as hypothermia and hypoxia. In this study, we showed that CIRP gene and protein levels were significantly increased in patients with COPD and in rats with chronic airway inflammation compared with healthy subjects. Similarly, inflammatory cytokine production and MUC5AC secretion were up-regulated in rats following cigarette smoke inhalation...
September 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27460104/endotracheal-tubes-cleaned-with-a-novel-mechanism-for-secretion-removal-a-randomized-controlled-clinical-study
#20
EDITORIAL
Riccardo Pinciroli, Cristina Mietto, Annop Piriyapatsom, Christopher T Chenelle, John G Thomas, Massimiliano Pirrone, Lynn Bry, Gregory R Wojtkiewicz, Matthias P Nahrendorf, Robert M Kacmarek, Lorenzo Berra
INTRODUCTION: Intubation compromises mucus clearance, allowing secretions to accumulate inside the endotracheal tube (ETT). The purpose of this trial was to evaluate a novel device for ETT cleaning. We hypothesized that its routine use would reduce tube occlusion due to mucus accumulation, while decreasing airway bacterial colonization. METHODS: Subjects were randomized to either the use of the device every 8 h, or the institutional standard of care (blind tracheal suction) only...
November 2016: Respiratory Care
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