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Airway mucus production and secretion

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https://www.readbyqxmd.com/read/28805732/the-mechanistic-links-between-insulin-and-cystic-fibrosis-transmembrane-conductance-regulator-cftr-cl-channel
#1
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/28618071/histamine-receptor-2-modifies-inkt-cell-activity-within-the-inflamed-lung
#2
R Ferstl, R Frei, W Barcik, E Schiavi, K Wanke, M Ziegler, N Rodriguez-Perez, D Groeger, P Konieczna, S Zeiter, D Nehrbass, R Lauener, C A Akdis, L O'Mahony
BACKGROUND: Histamine is a key immunoregulatory mediator and can dampen proinflammatory responses via activation of histamine receptor 2 (H2 R). The aim of this study was to determine the role of H2 R in modulating lung inflammatory responses. METHODS: H2 R was blocked using famotidine or activated using dimaprit in both the ovalbumin (OVA) and house dust mite extract (HDM) murine models of respiratory inflammation. H2 R-deficient animals and CD1d/H2 R-deficient animals were utilized to examine the CD1d presentation of lipid antigens (αGalCer or OCH) to invariant natural killer T (iNKT) cells...
June 15, 2017: Allergy
https://www.readbyqxmd.com/read/28578323/oxytetracycline-inhibits-mucus-secretion-and-inflammation-in-human-airway-epithelial-cells
#3
Said Ahmad Shah, Hajime Ishinaga, Kazuhiko Takeuchi
Oxytetracycline is a broad-spectrum antibiotic, but its nonantibacterial effects in the human respiratory tract are unknown. In this study, the effects of oxytetracycline on mucus secretion and inflammation were examined by PCR and ELISA in the human airway epithelial cell line NCI-H292. Oxytetracycline (10 μg/mL) significantly inhibited TNF-α-induced MUC5AC gene expression and MUC5AC protein levels in NCI-H292 cells. It also downregulated IL-8 and IL-1β gene expression and IL-1β protein levels. Our findings demonstrated that oxytetracycline suppressed mucus production and inflammation in human respiratory epithelial cells, providing further evidence for the usefulness of oxytetracycline for human airway inflammatory diseases...
June 3, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28543283/targeting-pp2a-and-proteasome-activity-ameliorates-features-of-allergic-airway-disease-in-mice
#4
P M Nair, M R Starkey, T J Haw, G Liu, J C Horvat, J C Morris, N M Verrills, A R Clark, A J Ammit, P M Hansbro
BACKGROUND: Asthma is an allergic airway disease (AAD) caused by aberrant immune responses to allergens. Protein phosphatase-2A (PP2A) is an abundant serine/threonine phosphatase with anti-inflammatory activity. The ubiquitin proteasome system (UPS) controls many cellular processes, including the initiation of inflammatory responses by protein degradation. We assessed whether enhancing PP2A activity with fingolimod (FTY720) or 2-amino-4-(4-(heptyloxy) phenyl)-2-methylbutan-1-ol (AAL(S) ), or inhibiting proteasome activity with bortezomib (BORT), could suppress experimental AAD...
May 24, 2017: Allergy
https://www.readbyqxmd.com/read/28531919/bupleurum-chinense-extract-ameliorates-an-ova-induced-murine-allergic-asthma-through-the-reduction-of-the-th2-and-th17-cytokines-production-by-inactivation-of-nf%C3%AE%C2%BAb-pathway
#5
Thi Tho Bui, Chun Hua Piao, Chang Ho Song, Hee Soon Shin, Ok Hee Chai
Bupleurum chinense belongs to the Bupleurum spp. family that has been used in traditional herbal medicine for over thousand years. It has been reported to have anti-inflammatory, anti-oxidant, hepato-protective, antipyretic, analgesic, anti-fibrotic and immunomodulatory effect. However, the effect of B. Chinense on allergic asthma remains unclear. This study investigated the immunomodulatory effects of B. Chinense extracts (BCE) on airway inflammation in asthmatic mice model. In the ovalbumin (OVA)-induced allergic asthma model, we evaluated the number of total cells, differential inflammatory cells and the production of proinflammatory cytokines in bronchoalveolar lavage fluid (BALF) and lung homogenate as well as histological structure...
July 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28470140/temporal-structure-function-variation-in-cultured-differentiated-human-nasal-epithelium-associated-with-acute-single-exposure-to-tobacco-smoke-or-e-cigarette-vapor
#6
Johnny L Carson, Laura Zhou, Luisa Brighton, Katherine H Mills, Haibo Zhou, Ilona Jaspers, Milan Hazucha
OBJECTIVE: Mucociliary clearance sustains a baseline functionality and an "on demand" capability to upregulate clearance upon irritant exposure involving mucus hypersecretion and accelerated ciliary beat frequency (CBF) modulated by nitric oxide (NO). This study characterized these elements as well as cellular and exogenous NO concentrations subsequent to a single exposure to tobacco smoke (TS) or e-cigarette vapor (EV) on cultured human airway epithelium. MATERIALS AND METHODS: Air-liquid interface (ALI) airway epithelial cultures per nonsmoking human subjects were subjected to single TS or EV exposures...
February 2017: Inhalation Toxicology
https://www.readbyqxmd.com/read/28420758/the-foxm1-inhibitor-rcm-1-suppresses-goblet-cell-metaplasia-and-prevents-il-13-and-stat6-signaling-in-allergen-exposed-mice
#7
Lifeng Sun, Xiaomeng Ren, I-Ching Wang, Arun Pradhan, Yufang Zhang, Hannah M Flood, Bo Han, Jeffrey A Whitsett, Tanya V Kalin, Vladimir V Kalinichenko
Goblet cell metaplasia and excessive mucus secretion associated with asthma, cystic fibrosis, and chronic obstructive pulmonary disease contribute to morbidity and mortality worldwide. We performed a high-throughput screen to identify small molecules targeting a transcriptional network critical for the differentiation of goblet cells in response to allergens. We identified RCM-1, a nontoxic small molecule that inhibited goblet cell metaplasia and excessive mucus production in mice after exposure to allergens...
April 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28129031/virus-like-particle-vaccines-containing-f-or-f-and-g-proteins-confer-protection-against-respiratory-syncytial-virus-without-pulmonary-inflammation-in-cotton-rats
#8
Hye Suk Hwang, Ki-Hye Kim, Youri Lee, Young-Tae Lee, Eun-Ju Ko, SooJin Park, Jong Seok Lee, Byung-Cheol Lee, Young-Man Kwon, Martin L Moore, Sang-Moo Kang
Vaccine-enhanced disease has been a major obstacle in developing a safe vaccine against respiratory syncytial virus (RSV). This study demonstrates the immunogenicity, efficacy, and safety of virus-like particle (VLP) vaccines containing RSV F (F VLP), G (G VLP), or F and G proteins (FG VLP) in cotton rats. RSV specific antibodies were effectively induced by vaccination of cotton rats with F VLP or FG VLP vaccines. After challenge, lung RSV clearance was observed with RSV F, G, FG VLP, and formalin inactivated RSV (FI-RSV) vaccines...
May 4, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28116959/immunomodulatory-indications-of-azithromycin-in-respiratory-disease-a-concise-review-for-the-clinician
#9
REVIEW
Cassondra L Cramer, Allie Patterson, Abdulrazak Alchakaki, Ayman O Soubani
Azithromycin has a well-characterized bacteriostatic activity. However, it also has a robust immunomodulatory effect that has proven beneficial in a variety of chronic illnesses. This effect results in decreased production of pro-inflammatory cytokines in the acute phase and promotes resolution of chronic inflammation in the later phases. Specifically, azithromycin has direct activity on airway epithelial cells to maintain their function and reduce mucus secretion. These characteristics have resulted in the use of azithromycin in the management of a variety of chronic lung diseases including chronic obstructive pulmonary disease, cystic fibrosis (CF), non-CF bronchiectasis, bronchiolitis obliterans syndrome, diffuse panbronchiolitis, and asthma...
June 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28115645/evaluating-the-toxicity-of-cigarette-whole-smoke-solutions-in-an-air-liquid-interface-human-in-vitro-airway-tissue-model
#10
Xuefei Cao, Levan Muskhelishvili, John Latendresse, Patricia Richter, Robert H Heflich
Exposure to cigarette smoke causes a multitude of pathological changes leading to tissue damage and disease. Quantifying such changes in highly differentiated in vitro human tissue models may assist in evaluating the toxicity of tobacco products. In this methods development study, well-differentiated human air-liquid-interface (ALI) in vitro airway tissue models were used to assess toxicological endpoints relevant to tobacco smoke exposure. Whole mainstream smoke solutions (WSSs) were prepared from 2 commercial cigarettes (R60 and S60) that differ in smoke constituents when machine-smoked under International Organization for Standardization conditions...
March 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28035597/identification-of-essential-genes-of-pseudomonas-aeruginosa-for-its-growth-in-airway-mucus
#11
COMPARATIVE STUDY
Mohammed Abd Alrahman, Sang Sun Yoon
Pseudomonas aeruginosa has been identified as an important causative agent of airway infection, mainly in cystic fibrosis. This disease is characterized by defective mucociliary clearance induced in part by mucus hyper-production. Mucin is a major component of airway mucus and is heavily O-glycosylated, with a protein backbone. Airway infection is known to be established with bacterial adhesion to mucin. However, the genes involved in mucin degradation or utilization remain elusive. In this study, we sought to provide a genetic basis of P...
January 2017: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/27992060/cb2-receptors-regulate-natural-killer-cells-that-limit-allergic-airway-inflammation-in-a-murine-model-of-asthma
#12
M E Ferrini, S Hong, A Stierle, D Stierle, N Stella, K Roberts, Z Jaffar
BACKGROUND: Allergic asthma is a chronic airway inflammatory disease involving the complementary actions of innate and adaptive immune responses. Endogenously generated cannabinoids acting via CB2 receptors play important roles in both homeostatic and inflammatory processes. However, the contribution of CB2-acting eicosanoids to the innate events preceding sensitization to the common house dust mite (HDM) allergen remains to be elucidated. We investigated the role of CB2 activation during allergen-induced pulmonary inflammation and natural killer (NK) cell effector function...
June 2017: Allergy
https://www.readbyqxmd.com/read/27865862/impaired-mucus-clearance-exacerbates-allergen-induced-type-2-airway-inflammation-in-juvenile-mice
#13
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
#14
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
#15
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
#16
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/27629364/selective-targeting-of-cbp-%C3%AE-catenin-inhibits-growth-of-and-extracellular-matrix-remodelling-by-airway-smooth-muscle
#17
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
https://www.readbyqxmd.com/read/27588910/interleukin-13-stimulates-muc5ac-expression-via-a-stat6-tmem16a-erk1-2-pathway-in-human-airway-epithelial-cells
#18
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
#19
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/27517516/s-allylmercapto-l-cysteine-modulates-muc5ac-and-aqp5-secretions-in-a-copd-model-via-nf-%C3%B0%C2%BAb-signaling-pathway
#20
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
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