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Airway mucus production and secretion

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https://www.readbyqxmd.com/read/29158154/tiotropium-inhibits-mucin-production-stimulated-by-neutrophil-elastase-but-not-by-il-13
#1
Kosaku Komiya, Shuichi Kawano, Isao Suzaki, Tomohiro Akaba, Jun-Ichi Kadota, Bruce K Rubin
Tiotropium, a muscarinic antagonist, is approved for the treatment of chronic obstructive pulmonary disease and poorly controlled asthma. Because mucus hypersecretion is characteristic of both of these diseases, and muscarinic agonists stimulate mucus secretion, we hypothesized that tiotropium would attenuate airway MUC5AC expression. We grew normal human bronchial epithelial (NHBE) cells to a goblet cell phenotype with 1 or 5 ng/mL of IL-13 and exposed these cells to 10 nM tiotropium or excipient for the full 14 days...
November 17, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29129801/activating-prostaglandin-e2-receptor-subtype-ep4-increases-secreted-mucin-from-airway-goblet-cells
#2
Tomohiro Akaba, Kosaku Komiya, Isao Suzaki, Yuji Kozaki, Jun Tamaoki, Bruce K Rubin
Prostaglandin E2 (PGE2) is a ligand of the E-type prostanoid receptors, EP1-4. PGE2 secretion is increased in the airways of patients with asthma by secretory phospholipases A2, which also increases MUC5AC mucin in goblet cells. We hypothesized that PGE2 would also increase MUC5AC mRNA and secreted protein through specific EP receptor activation. We sought to assess the effect of specific EP receptor activation on MUC5AC secretion from ciliated-enriched cells or goblet-enriched cells induced by IL-13. We develop an enriched goblet cell epithelium by growing normal human bronchial epithelial cells at air liquid interface for 14 days in the presence of IL-13...
November 9, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29099608/mucin-production-and-hydration-responses-to-mucopurulent-materials-in-normal-vs-cf-airway-epithelia
#3
Lubna H Abdullah, Raymond Coakley, Megan J Webster, Yunxiang Zhu, Robert Tarran, Giorgia Radicioni, Mehmet Kesimer, Richard C Boucher, C William Davis, Carla M P Ribeiro
RATIONALE: Cystic fibrosis (CF) airways disease produces a muco-obstructive lung phenotype characterized by airways mucus plugging, epithelial mucous cell metaplasia/hyperplasia, chronic infection and inflammation. Simultaneous biochemical and functional in vivo studies of mucin synthesis and secretion from CF airways are not available. In vitro translational models may quantitate differential CF vs. normal mucin and fluid secretory responses to infectious/inflammatory stimuli. OBJECTIVES: We tested the hypothesis that CF airways exhibit defective epithelial fluid, but not mucin, secretory responses to bacterial/inflammatory host products...
November 3, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29091392/thiol-benzo-triazolo-quinazolinone-covalently-modifies-alg44-to-inhibit-c-di-gmp-binding-and-reduces-alginate-production-by-pseudomonas-aeruginosa
#4
Eric Zhou, Anna B Seminara, Soo-Kyoung Kim, Cherisse L Hall, Yan Wang, Vincent T Lee
Pseudomonas aeruginosa is an opportunistic pathogen that affects a large proportion of cystic fibrosis (CF) patients. CF patients have dehydrated mucus within the airways that leads to the inability of the mucociliary escalator to expel inhaled microbes. Once inhaled, P. aeruginosa can persist in the lungs of the CF patients for the remainder of their lives. During this chronic infection, a phenomenon called mucoid conversion can occur in which P. aeruginosa can mutate and inactivate their mucA gene. As a consequence, transcription of the alg operon is highly expressed leading to the copious secretion of the alginate exopolysaccharide, which is associated with decreased lung function and increased CF patient morbidity and mortality...
November 1, 2017: ACS Chemical Biology
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/28932196/-epigallocatechin-3-gallate-reduces-cigarette-smoke-induced-airway-neutrophilic-inflammation-and-mucin-hypersecretion-in-rats
#6
Yingmin Liang, Kenneth W K Liu, Sze C Yeung, Xiang Li, Mary S M Ip, Judith C W Mak
Background: Cigarette smoking is the leading cause of chronic obstructive pulmonary disease. (-)-Epigallocatechin-3-gallate (EGCG), the major catechins in Chinese green tea, has been studied for its anti-oxidative and anti-inflammatory properties in cell and animal models. In this study, we aimed to analyze the effects of EGCG on cigarette smoke (CS)-induced airway inflammation and mucus secretion in the CS-exposed rat model. Methods: Male Sprague-Dawley rats were randomly divided into either sham air (SA) or CS exposure...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28918442/the-role-of-periostin-in-lung-fibrosis-and-airway-remodeling
#7
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
#8
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/28886691/impaired-response-of-the-bronchial-epithelium-to-inflammation-characterizes-severe-equine-asthma
#9
Laurence Tessier, Olivier Côté, Mary Ellen Clark, Laurent Viel, Andrés Diaz-Méndez, Simon Anders, Dorothee Bienzle
BACKGROUND: Severe equine asthma is a naturally occurring lung inflammatory disease of mature animals characterized by neutrophilic inflammation, bronchoconstriction, mucus hypersecretion and airway remodeling. Exacerbations are triggered by inhalation of dust and microbial components. Affected animals eventually are unable of aerobic performance. In this study transcriptomic differences between asthmatic and non-asthmatic animals in the response of the bronchial epithelium to an inhaled challenge were determined...
September 8, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28874459/protease-activated-receptor-2-activates-airway-apical-membrane-chloride-permeability-and-increases-ciliary-beating
#10
Derek B McMahon, Alan D Workman, Michael A Kohanski, Ryan M Carey, Jenna R Freund, Benjamin M Hariri, Bei Chen, Laurel J Doghramji, Nithin D Adappa, James N Palmer, David W Kennedy, Robert J Lee
Mucociliary clearance, driven by the engine of ciliary beating, is the primary physical airway defense against inhaled pathogens and irritants. A better understanding of the regulation of ciliary beating and mucociliary transport is necessary for identifying new receptor targets to stimulate improved clearance in airway diseases, such as cystic fibrosis and chronic rhinosinusitis. In this study, we examined the protease-activated receptor (PAR)-2, a GPCR previously shown to regulate airway cell cytokine and mucus secretion, and transepithelial Cl(-) current...
September 5, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28830530/prenatal-tobacco-smoke-exposure-predisposes-offspring-mice-to-exacerbated-allergic-airway-inflammation-associated-with-altered-innate-effector-function
#11
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/28815724/secreted-products-of-fasciola-hepatica-inhibit-the-induction-of-t-cell-responses-that-mediate-allergy
#12
C M Finlay, A M Stefanska, M M Coleman, H Jahns, J P Cassidy, R M McLoughlin, K H G Mills
There is evidence from epidemiology studies of a negative association between infection with helminth parasites and the development of allergy and asthma. Here, we demonstrate that the excretory/secretory products of the helminth Fasciola hepatica (FHES) protected mice against ovalbumin (OVA)-induced allergic asthma when administered at time of allergen sensitization. FHES reduced the accumulation of mucus, eosinophils and lymphocytes into the airways of allergen-challenged mice. Furthermore, FHES treatment suppressed Th2 responses in the airways...
August 16, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28805732/the-mechanistic-links-between-insulin-and-cystic-fibrosis-transmembrane-conductance-regulator-cftr-cl-channel
#13
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
#14
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
#15
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...
2017: Chemotherapy
https://www.readbyqxmd.com/read/28543283/targeting-pp2a-and-proteasome-activity-ameliorates-features-of-allergic-airway-disease-in-mice
#16
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
#17
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
#18
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
#19
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
#20
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
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