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Mechanism secretion of airways mucus

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https://www.readbyqxmd.com/read/29154907/an-integrated-mathematical-epithelial-cell-model-for-airway-surface-liquid-regulation-by-mechanical-forces
#1
Dan Wu, Richard C Boucher, Brian Button, Timothy Elston, Ching-Long Lin
A robust method based on reverse engineering was utilized to construct the ion-channel conductance functions for airway epithelial sodium channels (ENaC), the cystic fibrosis transmembrane conductance regulator (CFTR), and calcium-activated chloride channels (CaCC). The ion-channel conductance models for both normal (NL) and cystic fibrosis (CF) airway epithelia were developed and then coupled to an adenosine triphosphate (ATP) metabolism model and a fluid transport model (collectively called the integrated cell model) to investigate airway surface liquid (ASL) volume regulation and hence mucus concentration, by mechanical forces in NL and CF human airways...
November 15, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29102290/ion-channels-as-targets-to-treat-cystic-fibrosis-lung-disease
#2
S Lorraine Martin, Vinciane Saint-Criq, Tzyh-Chang Hwang, László Csanády
Lung health relies on effective mucociliary clearance and innate immune defence mechanisms. In cystic fibrosis (CF), an imbalance in ion transport due to an absence of chloride ion secretion, caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) and a concomitant sodium hyperabsorption, caused by dyregulation of the epithelial sodium channel (ENaC), results in mucus stasis which predisposes the lungs to cycles of chronic infection and inflammation leading to lung function decline...
October 25, 2017: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/28982736/an-epoxide-hydrolase-secreted-by-pseudomonas-aeruginosa-decreases-mucociliary-transport-and-hinders-bacterial-clearance-from-the-lung
#3
Kelli L Hvorecny, Emily Dolben, Sophie Moreau-Marquis, Thomas H Hampton, Tamer B Shabaneh, Becca A Flitter, Christopher D Bahl, Jennifer M Bomberger, Bruce D Levy, Bruce A Stanton, Deborah A Hogan, Dean R Madden
The opportunistic pathogen Pseudomonas aeruginosa colonizes the lungs of susceptible individuals by deploying virulence factors targeting host defenses. The secreted CFTR inhibitory factor (Cif) dysregulates the endocytic recycling of CFTR and thus reduces CFTR abundance in host epithelial membranes. We have postulated that the decrease in ion secretion mediated by Cif would slow mucociliary transport and decrease bacterial clearance from the lungs. To test this hypothesis, we explored the effects of Cif in cultured epithelia and in the lungs of mice...
October 5, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28944827/cerebral-ischemia-reperfusion-injury-induces-airway-mucus-hypersecretion-in-rats-and-activates-il%C3%A2-13%C3%A2-associated-inflammatory-mechanisms
#4
Baoning Xu, Lei Zhang, Yuqin Che, Chengyang Song, Wenjun Jiang, Jianhua Fan, Dali Tian
The majority of patients that suffer a stroke have excessive sputum, which accelerates the development of pulmonary complications. However, it is unclear whether cerebral ischemia and reperfusion (I/R) injury induces mucus hypersecretion, and the potential role of inflammation remains unknown. In the present study, the reversible middle cerebral artery occlusion model was applied in rats to induce cerebral I/R injury. The rats were grouped according to the duration of reperfusion (6, 12, 24, 48 and 72 h). Neurological dysfunction was evaluated by Longa scoring and lung dry‑to‑wet weight (dw/ww) ratios were determined to reflect the degree of mucus secretion...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28942146/leptin-positively-regulates-muc5ac-production-and-secretion-induced-by-interleukin-13-in-human-bronchial-epithelial-cells
#5
Wanming Hao, Jing Wang, Yu Zhang, Yunying Wang, Lixin Sun, Wei Han
Mucus hypersecretion and plugging of lower respiratory tract airways due to mucus plugs have long been recognized as the leading cause of the morbidity and mortality in asthma. MUC5AC protein is a major component of airway mucus. Here, we showed that interleukin (IL)-13 induced MUC5AC production and secretion, and leptin expression in the human bronchial epithelial cell line-16 (HBE16) cells in a concentration-dependent manner. Leptin knockdown suppressed MUC5AC production and secretion induced by IL-13. We further investigated the molecular mechanism by which leptin functioned, and found that leptin regulated IL-13-induced MUC5AC production and secretion via the JAK2-STAT3 pathway...
November 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28918442/the-role-of-periostin-in-lung-fibrosis-and-airway-remodeling
#6
REVIEW
David N O'Dwyer, Bethany B Moore
Periostin is a protein that plays a key role in development and repair within the biological matrix of the lung. As a matricellular protein that does not contribute to extracellular matrix structure, periostin interacts with other extracellular matrix proteins to regulate the composition of the matrix in the lung and other organs. In this review, we discuss the studies exploring the role of periostin to date in chronic respiratory diseases, namely asthma and idiopathic pulmonary fibrosis. Asthma is a major health problem globally affecting millions of people worldwide with significant associated morbidity and mortality...
December 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28894207/positive-feedback-of-the-amphiregulin-egfr-erk-pathway-mediates-pm2-5-from-wood-smoke-induced-muc5ac-expression-in-epithelial-cells
#7
Lingmei Huang, Jinding Pu, Fang He, Baoling Liao, Binwei Hao, Wei Hong, Xiuqin Ye, Jinglong Chen, Jun Zhao, Sha Liu, Juan Xu, Bing Li, Pixin Ran
Biomass fuel smoke is thought to contribute to chronic obstructive pulmonary disease, which is characterized by mucous cell metaplasia and enhanced mucus secretion. We investigated the effect of particulate matter (PM) with a diameter <2.5 μm (PM2.5) from wood smoke (WSPM2.5) on the expression of the most prominent secreted mucin, MUC5AC. Wood smoke was able to induce MUC5AC expression in the rat respiratory tract after 3 months of exposure. WSPM2.5 could induce MUC5AC production in both primary human airway epithelial cells and the NCI-H292 cell line...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28830530/prenatal-tobacco-smoke-exposure-predisposes-offspring-mice-to-exacerbated-allergic-airway-inflammation-associated-with-altered-innate-effector-function
#8
Maria Ferrini, Sophia Carvalho, Yoon Hee Cho, Britten Postma, Lucas Miranda Marques, Kent Pinkerton, Kevan Roberts, Zeina Jaffar
BACKGROUND: Epidemiological studies suggest that prenatal and early life environmental exposures have adverse effects on pulmonary function and are important contributors in the development of childhood asthma and allergic disease. The mechanism by which environmental tobacco smoke (ETS) exposure in utero promotes the development of allergic asthma remains unclear. In this study, we investigated the immunological consequences of prenatal exposure to ETS in order to understand events responsible for the development or exacerbation of allergic asthma...
August 22, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28805732/the-mechanistic-links-between-insulin-and-cystic-fibrosis-transmembrane-conductance-regulator-cftr-cl-channel
#9
REVIEW
Yoshinori Marunaka
The cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel belongs to the ATP-binding cassette (ABC) transporter superfamily and regulates Cl(-) secretion in epithelial cells for water secretion. Loss-of-function mutations to the CFTR gene cause dehydrated mucus on the apical side of epithelial cells and increase the susceptibility of bacterial infection, especially in the airway and pulmonary tissues. Therefore, research on the molecular properties of CFTR, such as its gating mechanism and subcellular trafficking, have been intensively pursued...
August 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28775098/influenza-virus-infection-alters-ion-channel-function-of-airway-and-alveolar-cells-mechanisms-and-physiological-sequelae
#10
James D Londino, Ahmed Lazrak, James F Collawn, Zsuzsanna Bebok, Kevin S Harrod, Sadis Matalon
The cystic fibrosis transmembrane conductance regulator (CFTR) and the amiloride-sensitive epithelial sodium channels (ENaC) are located in the apical membranes of airway and alveolar epithelial cells. These transporters play an important role in the regulation of lung fluid balance across airway and alveolar epithelia by being the conduits for chloride (Cl(-)) and bicarbonate (HCO3(-)) secretion and sodium (Na(+)) ion absorption, respectively. The functional role of these channels in the respiratory tract is to maintain the optimum volume and ionic composition of the bronchial pericilary fluid (PCL) and alveolar lining fluid (ALF) layers...
August 3, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28709893/regulatory-effect-of-baicalin-on-the-imbalance-of-th17-treg-responses-in-mice-with-allergic-asthma
#11
Lu Xu, Jinxia Li, Yu Zhang, Peng Zhao, Xuemei Zhang
ETHNOPHARMACOLOGY RELEVANCE: Baicalin, a flavonoid compound, was isolated from traditional Chinese medicine Scutellaria baicalensis Georgi. The study aimed to explore the regulatory effect of baicalin on immunological balance of Th17/Treg responses and the possible mechanisms in mice with allergic asthma. MATERIALS AND METHODS: Mice were sensitized and challenged with OVA+LPS by intranasal instillation, and were intragastrically treated with baicalin from days 22-36 after sensitization...
July 12, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28670393/chronic-intermittent-hypoxia-decreases-pulmonary-clearance-of-99m-tc-labelled-particulate-matter-in-mice
#12
Cuiping Fu, Huan Lu, Xu Wu, Jie Liu, Chengying Liu, Zilong Liu, Wei Yuan, Jian Zhou, Shanqun Li
BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) could cause systematic inflammation including pulmonary inflammatory response, whereas the influence of OSAHS in pulmonary clearance ability remains unknown. The main pathophysiological feature of OSAHS is chronic intermittent hypoxia (CIH). The goal of this study is to clarify the airway clearance of particulate matter (PM) in CIH mice, and to explore the potential mechanism. METHODS: Balb/c mice were divided into a CIH group and a control group, exposed to intermittent hypoxia and air chamber, respectively...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28662942/secretion-clearance-strategies-in-australian-and-new-zealand-intensive-care-units
#13
George Ntoumenopoulos, Naomi Hammond, Nicola R Watts, Kelly Thompson, Gabrielle Hanlon, Jennifer D Paratz, Peter Thomas
INTRODUCTION/AIMS: To describe the processes of care for secretion clearance in adult, intubated and mechanically ventilated patients in Australian and New Zealand Intensive Care Units (ICUs). METHODS/RESULTS: A prospective, cross-sectional study was conducted through the Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS CTG) Point Prevalence Program. Forty-seven ICUs collected data from 230 patients intubated and ventilated on the study day...
June 26, 2017: Australian Critical Care: Official Journal of the Confederation of Australian Critical Care Nurses
https://www.readbyqxmd.com/read/28658554/are-ilc2s-jekyll-and-hyde-in-airway-inflammation
#14
REVIEW
Kafi N Ealey, Kazuyo Moro, Shigeo Koyasu
Asthma is a complex heterogeneous disease of the airways characterized by lung inflammation, airway hyperreactivity (AHR), mucus overproduction, and remodeling of the airways. Group 2 innate lymphoid cells (ILC2s) play a crucial role in the initiation and propagation of type 2 inflammatory programs in allergic asthma models, independent of adaptive immunity. In response to allergen, helminths or viral infection, damaged airway epithelial cells secrete IL-33, IL-25, and thymic stromal lymphopoietin (TSLP), which activate ILC2s to produce type 2 cytokines such as IL-5, IL-13, and IL-9...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28566470/early-life-allergen-induced-mucus-overproduction-requires-augmented-neural-stimulation-of-pulmonary-neuroendocrine-cell-secretion
#15
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...
September 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
#16
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 Ca(2+)-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...
September 1, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28476309/bombesin-receptor-activated-protein-regulates-neutrophil-elastase-induced-mucin5ac-hypersecretion-in-human-bronchial-epithelial-cells
#17
Qing Xu, Ling-Xiu Chen, Dan-Hua Ran, Wen-Yue Xie, Qi Li, 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)...
August 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28397820/bitter-taste-receptor-agonists-mitigate-features-of-allergic-asthma-in-mice
#18
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
#19
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
#20
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...
November 2017: Mucosal Immunology
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