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mucus hyper secretion

Fengxia Ding, Bo Liu, Wenjing Zou, Daiyin Tian, Qubei Li, Jihong Dai, Zhengxiu Luo, Zhou Fu
BACKGROUND/AIMS: Previous studies have shown that lipopolysaccharide (LPS) exposure may have a protective effect on asthma by reducing airway hyper-responsiveness, airway inflammation and serum IgE levels. However, there are few studies investigating the effect of LPS on mucous secretion in asthma. In this study, we evaluate the relationship between LPS pre-treatment in infant mice and airway mucus hypersecretion in an OVA (ovalbumin)-induced asthma model, and further explore the mechanisms behind this effect...
2018: Cellular Physiology and Biochemistry
Steve Cornick, France Moreau, Herbert Y Gaisano, Kris Chadee
The intestinal mucosa encounters a barrage of ingested insults within the host yet under homeostasis elegantly facilitates nutrient absorption and sustenance of the commensal microbiota. An essential defence mechanism employed by the host is limiting the spatial niche various microbes may occupy as executed by the fluid mucus layer. Pathogens that violate their restricted niche within the intestinal mucosa are first expelled by robust mucus secretion from goblet cells thus by-passing the need for an immune response...
November 27, 2017: Microbial Cell
Lauren J Donoghue, Alessandra Livraghi-Butrico, Kathryn M McFadden, Joseph M Thomas, Gang Chen, Barbara R Grubb, Wanda K O'Neal, Richard C Boucher, Samir N P Kelada
Mucus hyper-secretion is a hallmark feature of asthma and other muco-obstructive airway diseases. The mucin proteins MUC5AC and MUC5B are the major glycoprotein components of mucus and have critical roles in airway defense. Despite the biomedical importance of these two proteins, the loci that regulate them in the context of natural genetic variation have not been studied. To identify genes that underlie variation in airway mucin levels, we performed genetic analyses in founder strains and incipient lines of the Collaborative Cross (CC) in a house dust mite mouse model of asthma...
October 2017: Genetics
L-L Liu, F-H Li, Y Zhang, X-F Zhang, J Yang
Asthma is a chronic allergic disease characterized by airway inflammation, airway hyper-responsiveness (AHR), and mucus hypersecretion. T-lymphocytes are involved in the pathogenesis of asthma, mediating airway inflammatory reactions by secreting cytokines. The phosphoinositide 3-kinase (PI3K) and Notch signaling pathways are associated with T cell signaling, proliferation, and differentiation, and are important in the progression of asthma. Thus, compounds that can modulate T cell proliferation and function may be of clinical value...
July 20, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
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
Caroline Sanden, Michiko Mori, Prajakta Jogdand, Jimmie Jönsson, Ravi Krishnan, Xiangdong Wang, Jonas S Erjefält
BACKGROUND: Th2 cytokines like interleukin-4, -5, and -13 are regarded as important drivers of the immunopathology underlying allergic rhinitis (AR) and asthma. The present study explores the capacity of pentosan polysulfate sodium (PPS), a semi-synthetic heparin-like macromolecular carbohydrate, to bind Th2 cytokines and exert biological neutralization in vitro, as well as anti-inflammatory actions in vivo. METHODOLOGY: The capacity of PPS to bind recombinant Th2 cytokines was tested with surface plasmon resonance (SPR) technology and biological Th2 neutralization was assessed by Th2-dependent proliferation assays...
September 2017: Immunity, Inflammation and Disease
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
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
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
Alison J May, Denis Headon, David P Rice, Alistair Noble, Abigail S Tucker
Hypertrophy, hyperplasia and altered mucus secretion from the respiratory submucosal glands (SMG) are characteristics of airway diseases such as cystic fibrosis, asthma and chronic bronchitis. More commonly, hyper-secretion of the nasal SMGs contributes to allergic rhinitis and upper airway infection. Considering the role of these glands in disease states, there is a significant dearth in understanding the molecular signals that regulate SMG development and patterning. Due to the imperative role of FGF signalling during the development of other branched structures, we investigated the role of Fgf10 during initiation and branching morphogenesis of murine nasal SMGs...
November 15, 2016: Developmental Biology
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
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...
January 14, 2016: Scientific Reports
Ji-Won Park, In-Chul Lee, Na-Rae Shin, Chan-Mi Jeon, Ok-Kyoung Kwon, Je-Won Ko, Jong-Choon Kim, Sei-Ryang Oh, In-Sik Shin, Kyung-Seop Ahn
Copper oxide nanoparticles (CuONPs), metal oxide nanoparticles were used in multiple applications including wood preservation, antimicrobial textiles, catalysts for carbon monoxide oxidation and heat transfer fluid in machines. We investigated the effects of CuONPs on the respiratory system in Balb/c mice. In addition, to investigate the effects of CuONPs on asthma development, we used a murine model of ovalbumin (OVA)-induced asthma. CuONPs markedly increased airway hyper-responsiveness (AHR), inflammatory cell counts, proinflammatory cytokines and reactive oxygen species (ROS)...
2016: Nanotoxicology
M de Vries, L Hesse, M R Jonker, M van den Berge, A J M van Oosterhout, I H Heijink, M C Nawijn
Most patients with allergic asthma are sensitized to house dust mite (HDM). The allergenicity of HDM largely depends on disruption of the integrity and proinflammatory activation of the airway epithelium. In this study, we hypothesized that Pim1 kinase activity attenuates HDM-induced asthma by preserving airway epithelial integrity. The effects of Pim1 kinase activity on barrier function and release of the proinflammatory mediators IL-1α and CCL20 were studied in vitro in 16HBE and primary bronchial epithelial cells (PBECs)...
December 1, 2015: American Journal of Physiology. Lung Cellular and Molecular Physiology
Tao Zhu, Xiao-Ling Wu, Wei Zhang, Min Xiao
Asthma is a common chronic pulmonary inflammatory disease, featured with mucus hyper-secretion in the airway. Recent studies found that glucagon like peptide-1 (GLP-1) analogs, including liraglutide and exenatide, possessed a potent anti-inflammatory property through a protein kinase A (PKA)-dependent signaling pathway. Therefore, the aim of current study was to investigate the value of GLP-1 analog therapy liraglutide in airway inflammation and mucus secretion in a murine model of ovalbumin (OVA)-induced asthma, and its underlying molecular mechanism...
2015: International Journal of Molecular Sciences
Bruce K Rubin
Airway mucus hypersecretion and secretion retention can result from inflammation, irritation, stimulation, or mucus-producing tumors. Secretion clearance can be furthered hampered by ciliary dysfunction and by weakness or restrictive lung disease, leading to an ineffective cough. There are a number of different mucoactive medications that have been used to reduce hypersecretion, make secretions easier to transport, or increase the efficiency of cough or mucus clearance. In this paper, I review the pathophysiology of secretory hyper-responsiveness and mucus hypersecretion and discuss the different aerosol medications that can be used to augment secretion clearance...
June 2015: Respiratory Care
Benjamin M Manning, Audrey F Meyer, Sarah M Gruba, Christy L Haynes
BACKGROUND: Asthma is a chronic inflammatory disease characterized by narrowed airways, bronchial hyper-responsiveness, mucus hyper-secretion, and airway remodeling. Mast cell (MC) infiltration into airway smooth muscle (ASM) is a defining feature of asthma, and ASM regulates the inflammatory response by secreting chemokines, including CXCL10 and CCL5. Single cell analysis offers a unique approach to study specific cellular signaling interactions within large and complex signaling networks such as the inflammatory microenvironment in asthma...
September 2015: Biochimica et Biophysica Acta
Katharina Maisel, Sumon Chattopadhyay, Thomas Moench, Craig Hendrix, Richard Cone, Laura M Ensign, Justin Hanes
Delivering drugs to the colorectum by enema has advantages for treating or preventing both local and systemic diseases. However, the properties of the enema itself are not typically exploited for improving drug delivery. Sodium ions are actively pumped out of the lumen of the colon, which is followed by osmotically-driven water absorption, so we hypothesized that this natural mechanism could be exploited to drive nanoparticles and drugs to the colorectal tissue surface. Here, we report that sodium-based, absorption-inducing (hypotonic) enemas rapidly transport hydrophilic drugs and non-mucoadhesive, mucus penetrating nanoparticles (MPP), deep into the colorectal folds to reach virtually the entire colorectal epithelial surface...
July 10, 2015: Journal of Controlled Release: Official Journal of the Controlled Release Society
Dan-Yang Zhou, Su-Rong Fang, Chun-Fang Zou, Qian Zhang, Wei Gu
Asthma is characterized by airway inflammation and airway remodeling. Our previous study revealed that grape seed proanthocyanidin extract (GSPE) could inhibit asthmatic airway inflammation and airway hyper-responsiveness by down-regulation of inducible nitric oxide synthase in a murine model of acute asthma. The present study aimed to evaluate GSPE's effects on airway inflammation and airway remodeling in a chronic asthmatic model. BALB/c mice were sensitized with ovalbumin (OVA) and then were challenged three times a week for 8 weeks...
February 2015: Natural Product Communications
Aran Singanayagam, Nicholas Glanville, Ross P Walton, Julia Aniscenko, Rebecca M Pearson, James W Pinkerton, Jay C Horvat, Philip M Hansbro, Nathan W Bartlett, Sebastian L Johnston
Viral exacerbations of chronic obstructive pulmonary disease (COPD), commonly caused by rhinovirus (RV) infections, are poorly controlled by current therapies. This is due to a lack of understanding of the underlying immunopathological mechanisms. Human studies have identified a number of key immune responses that are associated with RV-induced exacerbations including neutrophilic inflammation, expression of inflammatory cytokines and deficiencies in innate anti-viral interferon. Animal models of COPD exacerbation are required to determine the contribution of these responses to disease pathogenesis...
August 2015: Clinical Science (1979-)
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