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Mechanism secretion of airways mucus

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. We recently demonstrated that reduced mucociliary clearance, a characteristic feature of asthma, produces spontaneous type 2 airway inflammation in juvenile Scnn1b-transgenic (Scnn1b-Tg) mice. OBJECTIVE: 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
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...
November 5, 2016: International Immunopharmacology
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
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
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
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
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
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...
August 30, 2016: International Immunopharmacology
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
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
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...
July 26, 2016: Respiratory Care
Wei Du, Jinyu Su, Dan Ye, Yuegang Wang, Qiaobing Huang, Xiaowei Gong
Inhaled corticosteroids (ICS) are widely used to manage chronic obstructive pulmonary disease (COPD). However, withdrawal of ICS generally causes various adverse effects, warranting careful management of the ICS withdrawal. Pinellia ternata, a traditional Chinese herbal medicine, has been used to treat respiratory diseases in China for centuries. Here, we investigated its role in antagonizing ICS withdrawal-induced side effects, and explored the underlying mechanisms. The rat COPD model was established using a combination of passive cigarette smoking and intratracheal instillation of lipopolysaccharide (LPS)...
2016: American Journal of Chinese Medicine
Nathan A Zaidman, Angela Panoskaltsis-Mortari, Scott M O'Grady
Glucocorticoids strongly influence the mucosal-defense functions performed by the bronchial epithelium, and inhaled corticosteroids are critical in the treatment of patients with inflammatory airway diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. A common pathology associated with these diseases is reduced mucociliary clearance, a defense mechanism involving the coordinated transport of salt, water, and mucus by the bronchial epithelium, ultimately leading to retention of pathogens and particles in the airways and to further disease progression...
August 1, 2016: American Journal of Physiology. Cell Physiology
Raffaella Capasso, Mattia Carbone, Eugenio Rossi, Rosanna Mamone, Raffaele Zeccolini, Alfonso Reginelli, Massimo Zeccolini, Luca Brunese, Antonio Rotondo
BACKGROUND: Coughing is the most efficient mechanism for clearing mucus and fluid secretions from the airways and its reflex can be suppressed by sleep. Spontaneous tracheal ruptures are believed to result from raised intratracheal pressure against a closed glottis, such as for severe coughing. This is the first reported case of tracheal rupture presented on morning awakening after bronchial mucous plug formation during the nighttime sleep because of an ineffective cough reflex. CASE PRESENTATION: An otherwise healthy white 4-year-old child presented morning onset of dyspnea, chest pain and diffuse swelling of the neck...
2016: Journal of Medical Case Reports
Chuan-Qi Huang, Wei Li, Bo Wu, Wei-Ming Chen, Li-Hong Chen, Guan-Wen Mo, Qiu-Feng Zhang, Ling Gong, Jing Li, Hong-Chao Zhang, Hai-Mei Zhu, Qing-Zhong Zeng
ETHNOPHARMACOLOGICAL RELEVANCE AND AIM OF THE STUDY: Guang-Pheretima, the live form of the earthworm Pheretima aspergillum, is a traditional Chinese medicine commonly used for the treatment of asthma, cough, stroke, epilepsy and other diseases due to its anti-inflammatory, anti-asthmatic, anti-seizure, thrombolytic and diuretic properties. Although Guang-Pheretima is effective in the relief of asthma, its pharmacological activity and the underlying molecular mechanisms are not fully understood...
August 2, 2016: Journal of Ethnopharmacology
Xiaolei Ren, Shuangshuang Ma, Juan Wang, Simin Tian, Xiaorui Fu, Xinfeng Liu, Zhongfeng Li, Baosheng Zhao, Xueyong Wang
In order to compare the effect of dexamethasone and bergenin on chronic bronchitis and to reveal their anti-inflammatory mechanisms, (1)H NMR-based metabolomics was performed to explore the potential biomarkers of the disease and study the therapeutic mechanisms of the drugs. In this study, 40 Sprague-Dawley male rats were randomly divided into 4 groups, namely control, model, dexamethasone and bergenin groups, with 10 rats in each group. Except for the control group, rats from the other three groups were exposed to tobacco smoke for 1 h d(-1) for 28 days...
May 24, 2016: Molecular BioSystems
Wanting Xu, Ling Chen, Sheng Guo, Liangxia Wu, Jianhua Zhang
Asthma is a chronic inflammatory disorder, previous studies have shown that IL-17A contributes to the development of asthma, and there is a positive correlation between the level of IL-17A and the severity of disease. Here, we constructed recombinant Mycobacterium smegmatis expressing fusion protein Ag85A-IL-17A (rMS-Ag85a-IL-17a) and evaluated whether it could attenuate allergic airway inflammation, and further investigated the underlying mechanism. In this work, the murine model of asthma was established with ovalbumin, and mice were intranasally vaccinated with rMS-Ag85a-IL-17a...
2016: PloS One
Hui-Mei Wu, Qi-Ying Shen, Lei Fang, Shi-Hai Zhang, Pei-Ting Shen, Ya-Jing Liu, Rong-Yu Liu
Toll-like receptors (TLRs) play pivotal role in the pathogenesis of allergic airway diseases such as asthma. TLR9 is one of the most extensively studied TLRs as an approach to treat asthma. In this study, we investigated the role of TLR9 in the allergic airway inflammation and the underlying mechanism. Wild-type (WT) mice and TLR9(-/-) mice were sensitized and challenged with OVA to establish allergic airway disease model. We found that the expression of TLR9 was elevated concomitantly with airway inflammation post-OVA challenge, and TLR9 deficiency effectively inhibited airway inflammation, including serum OVA-specific immunoglobulin E (IgE), pulmonary inflammatory cell recruitment, mucus secretion, and bronchoalveolar lavage fluid (BALF) inflammatory cytokine production...
May 2016: Journal of Pineal Research
Shui-juan Zhang, Juan-xia Jiang, Qian-qian Ren, Yong-liang Jia, Jian Shen, Hui-juan Shen, Xi-xi Lin, Hong Lu, Qiang-min Xie
Ambroxol, a metabolite of bromhexine, is shown to exert several pharmacological activities, including secretolytic, anti-inflammatory and antioxidant actions. Oral and intravenous administration of ambroxol is useful for the airway inflammatory diseases. However, little is known about its potential in inhalation therapy for lipopolysaccharide (LPS)-induced mucous hypersecretion and inflammatory response. In the present study, we compared the pharmacological effects of ambroxol by inhalation with intravenous administration and preliminarily explored its mechanism of action...
March 15, 2016: European Journal of Pharmacology
Nam Soo Joo, Mauri E Krouse, Jae Young Choi, Hyung-Ju Cho, Jeffrey J Wine
In upper airways airway surface liquid (ASL) depth and clearance rates are both increased by fluid secretion. Secretion is opposed by fluid absorption, mainly via the epithelial sodium channel, ENaC. In static systems, increased fluid depth activates ENaC and decreased depth inhibits it, suggesting that secretion indirectly activates ENaC to reduce ASL depth. We propose an alternate mechanism in which cholinergic input, which causes copious airway gland secretion, also inhibits ENaC-mediated absorption. The conjoint action accelerates clearance, and the increased transport of mucus out of the airways restores ASL depth while cleansing the airways...
2016: Scientific Reports
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