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Airway mucus

Moyu Ming, Zhixi Luo, Shengqiu Lv, Chaoqian Li
The present study aimed to investigate whether inhalation of inactivated‑Mycobacterium phlei could prevent airway hyperresponsiveness and airway eosinophilia. A total of 24 male Balb/c mice were randomly divided into three groups: Normal control group (group A), asthma model group (group B) and the intervention group (group C), (8 mice/group). Group A mice were sensitized and with challenged saline and group B with ovalbumin (OVA). Group C mice were administered with aerosol Mycobacterium phlei once daily prior to the allergen challenge...
October 19, 2016: Molecular Medicine Reports
Hajime Ishinaga, Masako Kitano, Masaaki Toda, Corina N D'Alessandro-Gabazza, Esteban C Gabazza, Said Ahmad Shah, Kazuhiko Takeuchi
We investigated whether IL-33 is involved in mucus overproduction and goblet cell hyperplasia in eosinophilic chronic rhinosinusitis (ECRS). IL-33 mRNA was significantly higher in the eosinophilic CRS group than in the non-eosinophilic CRS group from human nasal polyps. IL-33 induced MUC5AC mRNA and MUC5AC protein, and also goblet cell hyperplasia at air liquid interface culture in human nasal epithelial cells. In addition to that, IL-33 induced MUC5B and FOXA3, and reduces FOXJmRNA. In conclusion, our present study demonstrated that the direct evidence of IL-33 which lead to increase mucin gene and protein expression, as well as goblet cell hyperplasia...
October 21, 2016: Cytokine
E C Economou, S Marinelli, M C Smith, A A Routt, V V Kravets, H W Chu, K Spendier, Z J Celinski
Superparamagnetic iron oxide (Fe3O4) and highly anisotropic barium hexaferrite (BaFe12O19) nanoparticles were coated with an anti-inflammatory drug and magnetically transported through mucus produced by primary human airway epithelial cells. Using wet planetary ball milling, dl-2-amino-3-phosphonopropionic acid-coated BaFe12O19 nano-particles (BaNPs) of 1-100 nm in diameter were prepared in water. BaNPs and conventional 20-30-nm Fe3O4 nanoparticles (FeNPs) were then encased in a polymer (PLGA) loaded with dexamethasone (Dex) and tagged for imaging...
September 2016: BioNanoScience
A J Byrne, M Weiss, S A Mathie, S A Walker, H L Eames, D Saliba, C M Lloyd, I A Udalova
Interferon regulatory factor 5 (IRF5) is a key transcription factor involved in the control of the expression of proinflammatory cytokine and responses to infection, but its role in regulating pulmonary immune responses to allergen is unknown. We used genetic ablation, adenoviral vector-driven overexpression, and adoptive transfer approaches to interrogate the role of IRF5 in pulmonary immunity and during challenge with the aeroallergen, house dust mite. Global IRF5 deficiency resulted in impaired lung function and extracellular matrix (ECM) deposition...
October 19, 2016: Mucosal Immunology
Richard L Blackmon, Silvia M Kreda, Patrick R Sears, Lawrence E Ostrowski, David B Hill, Brian S Chapman, Joseph B Tracy, Amy L Oldenburg
Mucus hydration (wt%) has become an increasingly useful metric in real-time assessment of respiratory health in diseases like cystic fibrosis and COPD, with higher wt% indicative of diseased states. However, available in vivo rheological techniques are lacking. Gold nanorods (GNRs) are attractive biological probes whose diffusion through tissue is sensitive to the correlation length of comprising biopolymers. Through employment of dynamic light scattering theory on OCT signals from GNRs, we find that weakly-constrained GNR diffusion predictably decreases with increasing wt% (more disease-like) mucus...
2016: Proceedings of SPIE
Juan Carlos Lopez-Rodriguez, Rodrigo Barderas, Mercedes Echaide, Jesus Perez-Gil, Mayte Villalba, Eva Batanero, Antonio Cruz
Aeroallergens are airborne substances -mainly proteins- capable of triggering Th2-immune responses in respiratory allergies. They enter into the body through the upper airways, reaching the mucosa afterwards. Mucosae lining at the luminal side consists of an epithelial barrier completely covered by mucus and pulmonary surfactant. Both, pulmonary surfactant and plasma membrane of the epithelial cells represent two physiological phospholipid-based barriers where allergens first impact before triggering their biological effects...
October 10, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
Hwan-Hee Jang, Su-Yeon Cho, Mi-Ju Kim, Jung-Bong Kim, Sung-Hyen Lee, Mee-Young Lee, Young-Min Lee
BACKGROUND: Asthma is an increasing global health problem, and novel strategies to prevent or ameliorate the condition are needed. Here, the effects of 80 % ethanol extracts of Salvia plebeia R. Br. (SE) on an induced inflammatory response were investigated. RESULTS: Salvia plebeia R. Br. inhibited production of pro-inflammatory cytokines, such as TNF-α and IL-6, as well as nitric oxide (NO) in LPS-stimulated RAW 264.7 cells. NO and pro-inflammatory cytokine production was suppressed more effectively by SE of the aerial parts (SE-A) than of the roots (SE-R) of S...
October 5, 2016: Biological Research
Fiorentina Roviezzo, Rosalinda Sorrentino, Valentina Mattera Iacono, Vincenzo Brancaleone, Michela Terlizzi, Maria Antonietta Riemma, Antonio Bertolino, Antonietta Rossi, Maria Matteis, Giuseppe Spaziano, Aldo Pinto, Bruno D'Agostino, Giuseppe Cirino
Compelling evidence suggests the involvement of sphingosine-1-phosphate (S1P) in the pathogenesis of asthma. The systemic administration of S1P causes asthma like features in the mouse involving mast cells. In this study we investigated whether disodium cromoglycate (DSCG), administered as a preventative treatment as in human therapy, could affect S1P effects on airways. BALB/c mice, treated with DSCG, received subcutaneous administration of S1P. Bronchi and pulmonary tissues were collected and functional, molecular and cellular studies were performed...
October 3, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Wu-Lin Zuo, Jing Yang, Kazunori Gomi, IonWa Chao, Ronald G Crystal, Renat Shaykhiev
The airway epithelium of cigarette smokers undergoes dramatic remodeling with hyperplasia of basal cells (BC) and mucus-producing cells, squamous metaplasia, altered ciliated cell differentiation and decreased junctional barrier integrity, relevant to chronic obstructive pulmonary disease and lung cancer. In this study, we show that EGFR ligand amphiregulin (AREG) is induced by smoking in human airway epithelium as a result of EGF-driven squamous differentiation of airway BC stem/progenitor cells. In turn, AREG induced a unique EGFR activation pattern in human airway BC, distinct from that evoked by EGF, leading to BC- and mucous hyperplasia, altered ciliated cell differentiation and impaired barrier integrity...
October 6, 2016: Stem Cells
Miaorong Yu, Jiuling Wang, Yiwei Yang, Chunliu Zhu, Qian Su, Shiyan Guo, Jiashu Sun, Yong Gan, Xinghua Shi, Huajian Gao
Mucus is a viscoelastic gel layer that typically protects exposed surfaces of the gastrointestinal (GI) tract, lung airways, and other mucosal tissues. Particles targeted to these tissues can be efficiently trapped and removed by mucus, thereby limiting the effectiveness of such drug delivery systems. In this study, we experimentally and theoretically demonstrated that cylindrical nanoparticles (NPs), such as mesoporous silica nanorods and calcium phosphate nanorods, have superior transport and trafficking capability in mucus compared with spheres of the same chemistry...
October 4, 2016: Nano Letters
S Vamsee Raju, Hyunki Kim, Stephen A Byzek, Li Ping Tang, John E Trombley, Patricia Jackson, Lawrence Rasmussen, J Michael Wells, Emily Falk Libby, Erik Dohm, Lindy Winter, Sharon L Samuel, Kurt R Zinn, J Edwin Blalock, Trenton R Schoeb, Mark T Dransfield, Steven M Rowe
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the US. The majority of COPD patients have symptoms of chronic bronchitis, which lacks specific therapies. A major impediment to therapeutic development has been the absence of animal models that recapitulate key clinical and pathologic features of human disease. Ferrets are well suited for the investigation of the significance of respiratory diseases, given prior data indicating similarities to human airway physiology and submucosal gland distribution...
September 22, 2016: JCI Insight
Lara Ravanetti, Annemiek Dijkhuis, Yanaika S Sabogal Pineros, Suzanne M Bal, Barbara S Dierdorp, Tamara Dekker, Adrian Logiantara, Ian M Adcock, Navin L Rao, Louis Boon, Gino Villetti, Peter J Sterk, Fabrizio Facchinetti, René Lutter
BACKGROUND: Acute worsening of asthma symptoms (exacerbation) is predominantly triggered by respiratory viruses, with influenza causing the most severe exacerbations. The lack of an adequate animal model hampers mechanistic insight and the development of new therapeutics. AIM: We developed and characterized a robust, consistent and reproducible mouse model of severe exacerbation of chronic allergic asthma. METHODS: Chronic allergic airway inflammation was induced following a house dust mite (HDM)-sensitization protocol...
October 3, 2016: Allergy
Isabelle Karine da Costa Nunes, Everton Tenório de Souza, Suzana Vanessa S Cardozo, Vinicius de Frias Carvalho, Nelilma Correia Romeiro, Patrícia Machado Rodrigues E Silva, Marco Aurélio Martins, Eliezer J Barreiro, Lídia Moreira Lima
Prior investigations showed that increased levels of cyclic AMP down-regulate lung inflammatory changes, stimulating the interest in phosphodiesterase (PDE)4 as therapeutic target. Here, we described the synthesis, pharmacological profile and docking properties of a novel sulfonamide series (5 and 6a-k) designed as PDE4 inhibitors. Compounds were screened for their selectivity against the four isoforms of human PDE4 using an IMAP fluorescence polarized protocol. The effect on allergen- or LPS-induced lung inflammation and airway hyper-reactivity (AHR) was studied in A/J mice, while the xylazine/ketamine-induced anesthesia test was employed as a behavioral correlate of emesis in rodents...
2016: PloS One
Nicholas Glanville, Tamlyn J Peel, Armin Schröder, Julia Aniscenko, Ross P Walton, Susetta Finotto, Sebastian L Johnston
Current understanding of adaptive immune, particularly T cell, responses to human rhinoviruses (RV) is limited. Memory T cells are thought to be of a primarily T helper 1 type, but both T helper 1 and T helper 2 memory cells have been described, and heightened T helper 2/ lessened T helper 1 responses have been associated with increased RV-induced asthma exacerbation severity. We examined the contribution of T helper 1 cells to RV-induced airways inflammation using mice deficient in the transcription factor T-Box Expressed In T Cells (Tbet), a critical controller of T helper 1 cell differentiation...
September 2016: PLoS Pathogens
Anja Lena Thiebes, Nicola Kelly, Caoimhe A Sweeney, Donnacha J McGrath, Johanna Clauser, Kathrin Kurtenbach, Valentine N Gesche, Weiluan Chen, Robbert Jan Kok, Ulrich Steinseifer, Mark Bruzzi, Barry J O'Brien, Peter E McHugh, Stefan Jockenhoevel, Christian G Cornelissen
Currently, there is no optimal treatment available for end stage tumour patients with airway stenosis. The PulmoStent concept aims on overcoming current hurdles in airway stenting by combining a nitinol stent with a nutrient-permeable membrane, which prevents tumour ingrowth. Respiratory epithelial cells can be seeded onto the cover to restore mucociliary clearance. In this study, a novel hand-braided dog bone stent was developed, covered with a polycarbonate urethane nonwoven and mechanically tested. Design and manufacturing of stent and cover were improved in an iterative process according to predefined requirements for permeability and mechanical properties and finally tested in a proof of concept animal study in sheep for up to 24 weeks...
September 27, 2016: Annals of Biomedical Engineering
Yutaka Shishikura, Akira Koarai, Hiroyuki Aizawa, Mutsuo Yamaya, Hisatoshi Sugiura, Mika Watanabe, Yuichiro Hashimoto, Tadahisa Numakura, Tomonori Makiguti, Kyoko Abe, Mituhiro Yamada, Toshiaki Kikuchi, Yasushi Hoshikawa, Yoshinori Okada, Masakazu Ichinose
BACKGROUND: In response to tissue damage or inflammation, adenosine-5'-triphosphate (ATP) is released into the extracellular compartment and has been demonstrated to augment inflammation via purinergic P2 receptors (P2Rs). Recently, ATP has been shown to be increased in the airways of COPD patients. In the present study, we examined the possible involvement of extracellular ATP in airway mucus hypersecretion during viral-induced COPD exacerbations. METHODS: The involvement of extracellular ATP in the release of a major airway mucin, MUC5AC, and its signal pathway was examined after stimulation with polyinosine-polycytidylic acid [poly(I:C)], a synthetic analog of dsRNA to mimic viral infection, and rhinovirus (RV) infection in NCI-H292 cells and differentiated airway epithelial cells from COPD patients...
September 27, 2016: Respiratory Research
Gregg A Duncan, James Jung, Justin Hanes, Jung Soo Suk
Recent evidence suggests that the airway mucus gel layer may be impermeable to the viral and synthetic gene vectors used in past inhaled gene therapy clinical trials for diseases like cystic fibrosis. These findings support the logic that inhaled gene vectors that are incapable of penetrating the mucus barrier are unlikely to provide meaningful benefit to patients. In this review, we discuss the biochemical and biophysical features of mucus that contribute its barrier function, and how these barrier properties may be reinforced in patients with lung disease...
September 20, 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
Yuan Lu, Qiong-Qiong Xing, Jian-Ya Xu, Dou Ding, Xia Zhao
Endoplasmic reticulum (ER) stress has been recently revealed to play a pivotal role in the pathogenesis of severe asthma. Astragalus polysaccharide (APS), a major bioactive component from Astragalus membranaceus, exerts immunomodulatory and anti-inflammatory effects and has been shown to suppress ER stress in chronic diseases such as type-2 diabetes. However, the pharmaceutical application of APS in the treatment of severe asthma is unknown. The results obtained here indicate that APS significantly attenuates eosinophils and neutrophil-dominant airway inflammation by reducing the mRNA levels of Cxcl5, Il8, and chemokine (C-C motif) ligand 20 (Ccl20) and the protein levels of IL13RA and IL17RA...
September 16, 2016: International Journal of Biological Macromolecules
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
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
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