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Mechanism secretion of airways mucus

Qian-Lin Yu, Zhangbo Chen
Asthma is a complex disease. The heterogeneity of airway inflammation during asthma indicates there are different mechanisms involved. In order to further study the mechanisms of asthma, different mouse models were established to mimic corresponding subtypes of asthma in clinic. Eosinophilic asthma was established by intraperitoneal injections of ovalbumin (OVA) on day 0 and day 7, followed by inhalation of aerosolized OVA on days 14-17. Neutrophilic asthma was established by transtracheal administration of a high dose of lipopolysaccharide (LPS; 10 µg) on days 15 and 17 in combination with OVA sensitization and challenge as described previously...
March 2018: Experimental and Therapeutic Medicine
Alison T Lennox, Stefanie L Coburn, John A Leech, Elisa M Heidrich, Thomas R Kleyman, Sally E Wenzel, Joseph M Pilewski, Timothy E Corcoran, Mike M Myerburg
Allergic airway disease is known to cause significant morbidity due to impaired mucociliary clearance, however the mechanism that leads to the mucus dysfunction is not entirely understood. Interleukin 13 (IL-13), a key mediator of Type 2 (T2) inflammation, profoundly alters the ion transport properties of airway epithelium. However, these electrophysiological changes cannot explain the thick, tenacious airway mucus that characterizes the clinical phenotype. Here we report that IL-13 dramatically increases the airway surface liquid (ASL) viscosity in cultured primary human bronchial epithelial cells and thereby inhibits mucus clearance...
February 1, 2018: Scientific Reports
Natalie Eva Nieuwenhuizen, Frank Kirstein, Jennifer Claire Hoving, Frank Brombacher
The precise mechanisms leading to development of T helper type (Th)2-driven allergic responses are unknown. We aimed to determine how IL-4 receptor alpha (IL-4Rα) signaling on CD11c+ cells influences allergen-induced Th2 responses in mice. CD11ccreIL-4Rα-/l°x mice, deficient in IL-4Rα on dendritic cells and alveolar macrophages, were compared to IL-4Rα-/l°x littermate controls in models of allergic airway disease induced by OVA/alum, OVA alone or house dust mite. Cytokine responses, eosinophil and neutrophil infiltration into the lungs, airway hyperreactivity and mucus hypersecretion were evaluated after allergen challenge...
January 17, 2018: Scientific Reports
Susan E Birket, Joy M Davis, Courtney M Fernandez, Katherine L Tuggle, Ashley M Oden, Kengyeh K Chu, Guillermo J Tearney, Michelle V Fanucchi, Eric J Sorscher, Steven M Rowe
The mechanisms underlying the development and natural progression of the airway mucus defect in cystic fibrosis (CF) remain largely unclear. New animal models of CF, coupled with imaging using micro-optical coherence tomography, can lead to insights regarding these questions. The Cftr-/- (KO) rat allows for longitudinal examination of the development and progression of airway mucus abnormalities. The KO rat exhibits decreased periciliary depth, hyperacidic pH, and increased mucus solid content percentage; however, the transport rates and viscoelastic properties of the mucus are unaffected until the KO rat ages...
January 11, 2018: JCI Insight
Hao Wang, Ting Yang, Tao Wang, Nanya Hao, Yongchun Shen, Yanqiu Wu, Zhicheng Yuan, Lei Chen, Fuqiang Wen
BACKGROUNDS: Cigarette smoke (CS)-induced airway mucus hypersecretion and inflammation are the prominent features of chronic obstructive pulmonary disease (COPD). As an anti-inflammatory flavonoid, phloretin was found to be involved in various inflammatory disorders such as sepsis. In this study, the effects of phloretin on CS-induced airway mucin secretion and inflammation were investigated in vivo and in vitro. METHODS: Phloretin dissolved in 1% DMSO was daily injected intraperitoneally to mice, which were then exposed to CS for four weeks...
December 12, 2017: International Immunopharmacology
Xiao-Hua Zhu, Qiu-Gen Li, Jun Wang, Guo-Zhu Hu, Zhi-Qiang Liu, Qing-Hua Hu, Gang Wu
OBJECTIVE: To investigate the molecular mechanism of action of BET bromodomain inhibitor JQ1 in treating airway remodeling in asthmatic mice. METHODS: A total of 24 mice were randomly divided into control group, ovalbumin (OVA)-induced asthma group (OVA group), and JQ1 intervention group (JQ1+OVA group), with 8 mice in each group. OVA sensitization/challenge was performed to establish a mouse model of asthma. At 1 hour before challenge, the mice in the JQ1+OVA group were given intraperitoneal injection of JQ1 solution (50 μg/g)...
December 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Zhimei Yang, Jianguo Zhuang, Lei Zhao, Xiuping Gao, Zhengxiu Luo, Enmei Liu, Fadi Xu, Zhou Fu
BACKGROUND: Asthma is characterized by chronic airway inflammation, airway hyperresponsiveness (AHR), and airway remodeling. While exposure of house dust mites (HDM) is a common cause of asthma, the pathogenesis of the HDM-induced asthma is not fully understood. Bronchopulmonary C-fibers (PCFs) contribute to the neurogenic inflammation, viral infection induced-persistent AHR, and ovalbumin induced collagen deposition largely via releasing neuropeptides, such as substance P (SP). However, PCF roles in the pathogenesis of the HDM-induced asthma remain unexplored...
November 29, 2017: Respiratory Research
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...
February 7, 2018: Journal of Theoretical Biology
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
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
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
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
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
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
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
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
James David 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 ([Formula: see text]) 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 periciliary fluid (PCL) and alveolar lining fluid (ALF) layers...
November 1, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
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
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
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
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