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Airway mucus production and secretion

Tim Koopmans, Stijn Crutzen, Mark H Menzen, Andrew J Halayko, Tillie-Louise Hackett, Darryl A Knight, Reinoud Gosens
BACKGROUND AND PURPOSE: Asthma is a heterogeneous chronic inflammatory disease, characterized by the development of structural changes (airway remodelling). β-catenin, a transcriptional co-activator is fundamentally involved in airway smooth muscle growth, and may be a potential target in the treatment of airway smooth muscle remodelling. EXPERIMENTAL APPROACH: Using small-molecule compounds that selectively target β-catenin breakdown or its interactions with transcriptional co-activators, we assessed their ability to inhibit airway smooth muscle remodelling in vitro and in vivo...
September 15, 2016: British Journal of Pharmacology
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...
August 17, 2016: Annals of Biomedical Engineering
Min Yang, Yongjie Wang, Yongchun Zhang, Fang Zhang, Zhongxi Zhao, Siying Li, Jianqiang Zhang, Xinke Cao, Daizhou Zhang
Garlic has shown versatile medicinal activities in the prevention and treatment of diseases such as chronic obstructive pulmonary disease (COPD). However, no individual garlic bioactive components have yet been determined in the COPD treatment effects. In this work, S-allylmercapto-l-cysteine (SAMC) identified in the aged garlic was selected as a model compound to determine its COPD therapeutic potential. The COPD model was established by using lipopolysaccharides (LPS) to stimulate the human airway submucosal gland cell line SPC-A1...
October 2016: International Immunopharmacology
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
Sang Baik Ye, Yoon Seok Choi, Yo Han Choi, Chang Hoon Bae, Yong-Woon Kim, So-Young Park, Si-Youn Song, Yong-Dae Kim
Objectives: Excessive production of mucus. Results.: in plugging of the airway tract, which can increase morbidity and mortality in affected patients. In patients with diabetes, inflammatory airway disease appears with more frequent relapse and longer duration of symptoms. However, the effects of high glucose (HG) on the secretion of mucin in inflammatory respiratory diseases are not clear. Therefore, this study was conducted in order to investigate the effect and the brief signaling pathway of HG on MUC5B expression in human airway epithelial cells...
July 7, 2016: Clinical and Experimental Otorhinolaryngology
Naomi A Mckoy, Lisa M Wilson, Ian J Saldanha, Olaide A Odelola, Karen A Robinson
BACKGROUND: People with cystic fibrosis experience chronic airway infections as a result of mucus build up within the lungs. Repeated infections often cause lung damage and disease. Airway clearance therapies aim to improve mucus clearance, increase sputum production, and improve airway function. The active cycle of breathing technique (also known as ACBT) is an airway clearance method that uses a cycle of techniques to loosen airway secretions including breathing control, thoracic expansion exercises, and the forced expiration technique...
2016: Cochrane Database of Systematic Reviews
Etsuko Tagaya, Osamitsu Yagi, Akitoshi Sato, Ken Arimura, Kiyoshi Takeyama, Mitsuko Kondo, Jun Tamaoki
BACKGROUND: Increased sputum production is an important feature of COPD, in which a large amount of secretions stagnated in the respiratory lumen may aggravate airflow limitation, impair airway mucociliary transport, and cause recurrent respiratory infection and, hence, acute exacerbations of the diseases. There is evidence that airway mucus hypersecretion is associated with the severity and prognosis of COPD, but the symptoms are generally difficult to treat. METHODS: In an open, non-controlled study, we examined the effect of the anticholinergic agent tiotropium on airway mucus hypersecretion in 22 COPD patients...
August 2016: Pulmonary Pharmacology & Therapeutics
Cheng-Chi Chan, Chin-Wen Lai, Chia-Jen Wu, Li-Chen Chen, Mi-Hua Tao, Ming-Ling Kuo
Allergic airway inflammation driven by T helper 2 (Th2)-type immunity is characterized by airway hyperresponsiveness, eosinophilic infiltration, and elevated IgE production. Various novel strategies for managing asthma have been explored, such as DNA vaccines, T-cell peptides, and allergen-specific immunotherapy. A principal goal of most immunotherapeutic approaches is active and long-term allergen-specific tolerance. Liver-specific gene transfer using adeno-associated virus (AAV) has been shown to favorably induce tolerogenic responses to therapeutic products in various experimental models...
August 2016: Human Gene Therapy
Caroline Ridley, Sara Kirkham, Sally J Williamson, C William Davis, Philip Woodman, David J Thornton
MUC5B is a major polymeric mucin in the airway mucus gel and is an essential component of innate defense of the respiratory epithelium. Knowledge of the synthesis and intracellular processing of MUC5B is incomplete. We investigated the molecular details of MUC5B assembly in primary human bronchial epithelial cells (HBECs) grown at an air-liquid interface (ALI). Electrophoretic and centrifugal separations of intracellular forms of MUC5B probed with antibodies specific for non-O-glycosylated and O-glycosylated forms of the mucin identified three major intracellular populations of MUC5B (non-O-glycosylated monomer and dimer, and O-glycosylated polymers)...
May 15, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
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
Kumiko Takezawa, Takao Ogawa, Shino Shimizu, Takeshi Shimizu
BACKGROUND: Mucus hypersecretion and neutrophil infiltration are important characteristics of airway inflammation. Epidermal growth factor receptor (EGFR) transactivation induces mucus and inflammatory cytokine secretion from airway epithelial cells. To elucidate the roles of EGFR in airway inflammation, the in vitro effects on mucin production and interleukin (IL) 8 secretion from cultured airway epithelial cells and the in vivo effects on mucus hypersecretion and neutrophil infiltration in rat nasal mucosa of the EGFR tyrosine kinase inhibitor AG1478 were examined...
January 2016: American Journal of Rhinology & Allergy
Ivan M Lang, Steven T Haworth, Bidyut K Medda, Hubert Forster, Reza Shaker
Acid in the esophagus causes airway constriction, tracheobronchial mucous secretion, and a decrease in tracheal mucociliary transport rate. This study was designed to investigate the neuropharmacological mechanisms controlling these responses. In chloralose-anesthetized cats (n = 72), we investigated the effects of vagotomy or atropine (100 μg·kg(-1)·30 min(-1) iv) on airway responses to esophageal infusion of 0.1 M PBS or 0.1 N HCl at 1 ml/min. We quantified 1) diameter of the bronchi, 2) tracheobronchial mucociliary transport rate, 3) tracheobronchial mucous secretion, and 4) mucous content of the tracheal epithelium and submucosa...
April 1, 2016: Journal of Applied Physiology
Riccardo Ghidoni, Anna Caretti, Paola Signorelli
Sphingolipid bioactivities in the respiratory airways and the roles of the proteins that handle them have been extensively investigated. Gas or inhaled particles or microorganisms come into contact with mucus components, epithelial cells, blood barrier, and immune surveillance within the airways. Lung structure and functionality rely on a complex interplay of polar and hydrophobic structures forming the surfactant layer and governing external-internal exchanges, such as glycerol-phospholipids sphingolipids and proteins...
2015: Mediators of Inflammation
J C Coltherd, D T Rodgers, R E Lawrie, L Al-Riyami, C J Suckling, W Harnett, M M Harnett
Chronic asthma is associated with persistent lung inflammation and long-term remodelling of the airways that have proved refractory to conventional treatments such as steroids, despite their efficacy in controlling acute airway contraction and bronchial inflammation. As its recent dramatic increase in industrialised countries has not been mirrored in developing regions, it has been suggested that helminth infection may protect humans against developing asthma. Consistent with this, ES-62, an immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, can prevent pathology associated with chronic asthma (cellular infiltration of the lungs, particularly neutrophils and mast cells, mucus hyper-production and airway thickening) in an experimental mouse model...
2016: Scientific Reports
Kenji Izuhara, Simon J Conway, Bethany B Moore, Hisako Matsumoto, Cecile T J Holweg, John G Matthews, Joseph R Arron
Periostin is a matricellular protein that has been implicated in many disease states. It interacts with multiple signaling cascades to modulate the expression of downstream genes that regulate cellular interactions within the extracellular matrix. This review focuses on the role of periostin in respiratory diseases, including asthma and idiopathic pulmonary fibrosis, and its potential to help guide treatment or assess prognosis. Epithelial injury is a common feature of many respiratory diseases, resulting in the secretion, among others, of periostin, which is subsequently involved in airway remodeling and other aspects of pulmonary pathophysiology...
May 1, 2016: American Journal of Respiratory and Critical Care Medicine
Emily V S Ha, Duncan F Rogers
BACKGROUND: In asthma and chronic obstructive pulmonary disease (COPD), airway mucus hypersecretion contributes to impaired mucociliary clearance, mucostasis and, potentially, the development of mucus plugging of the airways. SUMMARY: Excess mucus production can be targeted via therapies that focus on inhibition mucin synthesis, via reducing expression of mucin (MUC) genes, and/or inhibition of mucin secretion into the airways. KEY MESSAGES: This review discusses a number of therapeutic approaches to reduce airway mucus in asthma and COPD, including the use of synthetic and natural products...
2016: Pharmacology
Sin-Hye Park, Ju-Hyun Gong, Yean-Jung Choi, Min-Kyung Kang, Yun-Ho Kim, Young-Hee Kang
Mucus hypersecretion is an important pathological feature of chronic airway diseases, such as asthma and pulmonary diseases. MUC5AC is a major component of the mucus matrix forming family of mucins in the airways. The initiation of endoplasmic reticulum (ER)-mediated stress responses contributes to the pathogenesis of airway diseases. The present study investigated that ER stress was responsible for airway mucus production and this effect was blocked by the flavonoid kaempferol. Oral administration of ≥10 mg/kg kaempferol suppressed mucus secretion and goblet cell hyperplasia observed in the bronchial airway and lung of BALB/c mice sensitized with ovalbumin (OVA)...
2015: PloS One
Kei Mishina, Masaharu Shinkai, Tadasuke Shimokawaji, Akimichi Nagashima, Yusuke Hashimoto, Yoriko Inoue, Yoshiaki Inayama, Bruce K Rubin, Yoshiaki Ishigatsubo, Takeshi Kaneko
Mucus hypersecretion and goblet cell hyperplasia are common features that characterize asthma. IL-13 increases mucin (MUC) 5AC, the major component of airway mucus, in airway epithelial cells. According to the literature, IL-13 receptor activation leads to STAT6 activation and consequent induction of chloride channel accessory 1 (CLCA1) gene expression, associated with the induction of MUC5AC. Heme oxygenase-1 (HO-1) is an enzyme that catalyzes oxidation of heme to biliverdin, and has anti-inflammatory and anti-oxidant properties...
December 2015: International Immunopharmacology
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