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https://www.readbyqxmd.com/read/28108847/airway-mucus-inflammation-and-remodeling-emerging-links-in-the-pathogenesis-of-chronic-lung-diseases
#1
REVIEW
Zhe Zhou-Suckow, Julia Duerr, Matthias Hagner, Raman Agrawal, Marcus A Mall
Airway mucus obstruction is a hallmark of many chronic lung diseases including rare genetic disorders such as cystic fibrosis (CF) and primary ciliary dyskinesia, as well as common lung diseases such as asthma and chronic obstructive pulmonary disease (COPD), which have emerged as a leading cause of morbidity and mortality worldwide. However, the role of excess airway mucus in the in vivo pathogenesis of these diseases remains poorly understood. The generation of mice with airway-specific overexpression of epithelial Na(+) channels (ENaC), exhibiting airway surface dehydration (mucus hyperconcentration), impaired mucociliary clearance (MCC) and mucus plugging, led to a model of muco-obstructive lung disease that shares key features of CF and COPD...
January 20, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28108561/semaphorin-3e-deficiency-exacerbates-airway-inflammation-hyperresponsiveness-and-remodeling-in-a-mouse-model-of-allergic-asthma
#2
Hesam Movassagh, Lianyu Shan, Ashfaque Mohammed, Andrew J Halayko, Abdelilah S Gounni
Semaphorin 3E (Sema3E) plays a crucial role in axon guidance, vascular patterning, and immune regulation. Nevertheless, the role of Sema3E in asthma is still elusive. In this study, we show that genetic ablation of Sema3E in mice results in increased lung granulocytosis, airway hyperresponsiveness, mucus overproduction, collagen deposition, and Th2/Th17 inflammation. Transfer of Sema3e(-/-) bone marrow progenitor cells to irradiated wild-type (WT) recipients exacerbates airway hyperresponsiveness and inflammation, whereas transfer of WT bone marrow progenitor cells ameliorates asthma pathology in Sema3e(-/-) recipients...
January 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28107494/protective-roles-for-rgs2-in-a-mouse-model-of-house-dust-mite-induced-airway-inflammation
#3
Tresa George, Matthew Bell, Mainak Chakraborty, David P Siderovski, Mark A Giembycz, Robert Newton
The GTPase-accelerating protein, regulator of G-protein signalling 2 (RGS2) reduces signalling from G-protein-coupled receptors (GPCRs) that signal via Gαq. In humans, RGS2 expression is up-regulated by inhaled corticosteroids (ICSs) and long-acting β2-adrenoceptor agonists (LABAs) such that synergy is produced in combination. This may contribute to the superior clinical efficacy of ICS/LABA therapy in asthma relative to ICS alone. In a murine model of house dust mite (HDM)-induced airways inflammation, three weeks of intranasal HDM (25 μg, 3×/week) reduced lung function and induced granulocytic airways inflammation...
2017: PloS One
https://www.readbyqxmd.com/read/28107345/syk-regulates-neutrophilic-airway-hyper-responsiveness-in-a-chronic-mouse-model-of-allergic-airways-inflammation
#4
Sepehr Salehi, Xiaomin Wang, Stephen Juvet, Jeremy A Scott, Chung-Wai Chow
BACKGROUND: Asthma is a chronic inflammatory disease characterized by airways hyper-responsiveness (AHR), reversible airway obstruction, and airway inflammation and remodeling. We previously showed that Syk modulates methacholine-induced airways contractility in naïve mice and in mice with allergic airways inflammation. We hypothesize that Syk plays a role in the pathogenesis of AHR; this was evaluated in a chronic 8-week mouse model of house dust mite (HDM)-induced allergic airways inflammation...
2017: PloS One
https://www.readbyqxmd.com/read/28106744/oligonucleotide-therapy-for-obstructive-and-restrictive-respiratory-diseases
#5
REVIEW
Wupeng Liao, Jinrui Dong, Hong Yong Peh, Lay Hong Tan, Kah Suan Lim, Li Li, Wai-Shiu Fred Wong
Inhaled oligonucleotide is an emerging therapeutic modality for various common respiratory diseases, including obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD) and restrictive airway diseases like idiopathic pulmonary fibrosis (IPF). The advantage of direct accessibility for oligonucleotide molecules to the lung target sites, bypassing systemic administration, makes this therapeutic approach promising with minimized potential systemic side effects. Asthma, COPD, and IPF are common chronic respiratory diseases, characterized by persistent airway inflammation and dysregulated tissue repair and remodeling, although each individual disease has its unique etiology...
January 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28103897/dual-rna-seq-reveals-viral-infections-in-asthmatic-children-without-respiratory-illness-which-are-associated-with-changes-in-the-airway-transcriptome
#6
Agata Wesolowska-Andersen, Jamie L Everman, Rebecca Davidson, Cydney Rios, Rachelle Herrin, Celeste Eng, William J Janssen, Andrew H Liu, Sam S Oh, Rajesh Kumar, Tasha E Fingerlin, Jose Rodriguez-Santana, Esteban G Burchard, Max A Seibold
BACKGROUND: Respiratory illness caused by viral infection is associated with the development and exacerbation of childhood asthma. Little is known about the effects of respiratory viral infections in the absence of illness. Using quantitative PCR (qPCR) for common respiratory viruses and for two genes known to be highly upregulated in viral infections (CCL8/CXCL11), we screened 92 asthmatic and 69 healthy children without illness for respiratory virus infections. RESULTS: We found 21 viral qPCR-positive and 2 suspected virus-infected subjects with high expression of CCL8/CXCL11...
January 19, 2017: Genome Biology
https://www.readbyqxmd.com/read/28102118/myeloid-cells-in-asthma
#7
Bart N Lambrecht, Emma K Persson, Hamida Hammad
Asthma is a heterogeneous chronic inflammatory disorder of the airways, and not surprisingly, many myeloid cells play a crucial role in pathogenesis. Antigen-presenting dendritic cells are the first to recognize the allergens, pollutants, and viruses that are implicated in asthma pathogenesis, and subsequently initiate the adaptive immune response by migrating to lymph nodes. Eosinophils are the hallmark of type 2 inflammation, releasing toxic compounds in the airways and contributing to airway remodeling. Mast cells and basophils control both the early- and late-phase allergic response and contribute to alterations in smooth muscle reactivity...
January 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28100228/association-of-stem-cell-factor-gene-expression-with-severity-and-atopic-state-in-patients-with-bronchial-asthma
#8
Safaa I Tayel, Sally M El-Hefnway, Eman M Abd El Gayed, Gehan A Abdelaal
BACKGROUND: Bronchial asthma is a chronic inflammatory and remodeling disorder of the airways, in which many cells, cellular elements, and cytokines play important roles. Stem cell factor (SCF) may contribute to the inflammatory changes occurring in asthma. We aimed to show the expression of SCF gene in patients with asthma as a means of diagnosis and its association with severity and atopic state in these patients. METHODS: This study was carried out on 80 subjects, 50 asthmatic patients and 30 age and gender matched healthy control persons...
January 18, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28099113/rage-deficiency-predisposes-mice-to-virus-induced-paucigranulocytic-asthma
#9
Jaisy Arikkatt, Md Ashik Ullah, Kirsty Renfree Short, Vivan Zhang, Wan Jun Gan, Zhixuan Loh, Rhiannon B Werder, Jennifer Simpson, Peter D Sly, Stuart B Mazzone, Kirsten M Spann, Manuel Ar Ferreira, John W Upham, Maria B Sukkar, Simon Phipps
Asthma is a chronic inflammatory disease. Although many patients with asthma develop type-2 dominated eosinophilic inflammation, a number of individuals develop paucigranulocytic asthma, which occurs in the absence of eosinophilia or neutrophilia. The aetiology of paucigranulocytic asthma is unknown. However, both respiratory syncytial virus (RSV) infection and mutations in the receptor for advanced glycation endproducts (RAGE) are risk factors for asthma development. Here, we show that RAGE deficiency impairs anti-viral immunity during an early-life infection with pneumonia virus of mice (PVM; a murine analogue of RSV)...
January 18, 2017: ELife
https://www.readbyqxmd.com/read/28091773/the-nervous-system-of-airways-and-its-remodeling-in-inflammatory-lung-diseases
#10
REVIEW
Katrin Julia Audrit, Lucas Delventhal, Öznur Aydin, Christina Nassenstein
Inflammatory lung diseases are associated with bronchospasm, cough, dyspnea and airway hyperreactivity. The majority of these symptoms cannot be primarily explained by immune cell infiltration. Evidence has been provided that vagal efferent and afferent neurons play a pivotal role in this regard. Their functions can be altered by inflammatory mediators that induce long-lasting changes in vagal nerve activity and gene expression in both peripheral and central neurons, providing new targets for treatment of pulmonary inflammatory diseases...
January 14, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28089919/an-orally-active-geranyl-acetophenone-attenuates-airway-remodeling-in-a-murine-model-of-chronic-asthma
#11
Yu Zhao Lee, Khozirah Shaari, Manraj Singh Cheema, Chau Ling Tham, Mohd Roslan Sulaiman, Daud Ahmad Israf
2,4,6-Trihydroxy-3-geranyl acetophenone (tHGA) is a synthetic compound that is naturally found in Melicope ptelefolia. We had previously demonstrated that parenteral administration of tHGA reduces pulmonary inflammation in OVA-sensitized mice. In this study, we evaluated the effect of orally administered tHGA upon airway remodeling in a murine model of chronic asthma. Female BALB/C mice were sensitized intraperitoneally with ovalbumin (OVA) on day 0, 7 and 14, followed by aerosolized 1% OVA 3 times per week for 6 weeks...
January 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28088960/-role-and-mechanism-of-hydrogen-sulfide-in-cigarette-smoke-induced-chronic-obstructive-pulmonary-disease-related-pulmonary-vascular-remodeling-in-rats
#12
M X Li, Y H Chen, C C Liao, F Lin, Y Bai, W J Mi, Y Sun, Y F Qi
Objective: To investigate the role and mechanism of hydrogen sulfide (H2S) in rats with chronic obstructive pulmonary disease (COPD) related pulmonary vascular remodeling. Methods: Twenty four healthy male Sprague-Dawley rats were randomly divided into 4 groups: control group, cigarette smoke (CS) group, CS+ Sodium hydrosulfide (NaHS) group and CS+ DL-propargylglycine (PPG) group. Rats in control group were fed normally and breathed clear air, and for the rest groups, passive cigarette smoke inhalation method were adopted to establish COPD model...
January 10, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28076322/aeroallergen-der-p-2-promotes-motility-of-human-non-small-cell-lung-cancer-cells-via-toll-like-receptor-mediated-up-regulation-of-urokinase-type-plasminogen-activator-and-integrin-focal-adhesion-kinase-signaling
#13
Chun-Hsiang Lin, Hui-Han Lin, Cheng-Yi Kuo, Shao-Hsuan Kao
House dust mite (HDM) allergens are one of the major causes leading to respiratory hypersensitiveness and airway remodeling. Here we hypothesized that a major HDM allergen Der p 2 could increase cell motility and invasiveness of non-small cell lung cancer (NSCLC) cells. Our results showed that low dose (1 and 3 μg/mL) recombinant Der p 2 protein (DP2) enhanced the migration and invasiveness of human NSCLC cell A549, H1299 and CL1-5, but nonsignificantly altered their growth. Further investigation revealed that integrin αV level was increased and its downstream signaling including focal adhesion kinase (FAK) and paxillin were activated in A549 cells exposed to DP2...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28073835/mechanosensitive-transient-receptor-potential-vanilloid-4-regulates-dermatophagoides-farinae-induced-airway-remodeling-via-2-distinct-pathways-modulating-matrix-synthesis-and-degradation
#14
Farai Gombedza, Vinay Kondeti, Nosayba Al-Azzam, Stephanie Koppes, Ernest Duah, Prachi Patil, Madison Hexter, Daniel Phillips, Charles K Thodeti, Sailaja Paruchuri
Contributions of mechanical signals to airway remodeling during asthma are poorly understood. Transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel, has been implicated in cardiac and pulmonary fibrosis; however, its role in asthma remains elusive. Employing a Dermatophagoides farinae-induced asthma model, we report here that TRPV4 knockout mice were protected from D. farinae-induced airway remodeling. Furthermore, lung fibroblasts that were isolated from TRPV4 knockout mice showed diminished differentiation potential compared with wild-type mice...
January 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28066584/overexpression-of-farnesoid-x-receptor-in-small-airways-contributes-to-epithelial-to-mesenchymal-transition-and-cox-2-expression-in-chronic-obstructive-pulmonary-disease
#15
Bi Chen, Wen-Jie You, Shan Xue, Hui Qin, Xu-Ji Zhao, Miao Zhang, Xue-Qing Liu, Shu-Yang Zhu, Han-Dong Jiang
BACKGROUND: Epithelial-mesenchymal transition (EMT) and cyclooxygenase-2 (COX-2) contribute to airway remodelling and inflammation in chronic obstructive pulmonary disease (COPD). Recent data suggest that the farnesoid X receptor (FXR), a nuclear receptor traditionally considered as bile acid-activated receptor, is also expressed in non-classical bile acids target tissues with novel functions beyond regulating bile acid homeostasis. This study aimed to investigate the potential role of FXR in the development of COPD, as well as factors that affect FXR expression...
November 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28063043/subcutaneous-and-sublingual-immunotherapy-in-a-mouse-model-of-allergic-asthma
#16
Laura Hesse, Martijn C Nawijn
Allergic asthma, caused by inhaled allergens such as house dust mite or grass pollen, is characterized by reversible airway obstruction, associated with an eosinophilic inflammation of the airways, as well as airway hyper responsiveness and remodeling. The inhaled allergens trigger a type-2 inflammatory response with involvement of innate lymphoid cells (ILC2) and Th2 cells, resulting in high production of immunoglobulin E (IgE) antibodies. Consequently, renewed allergen exposure results in a classic allergic response with a distinct early and late phase, both resulting in bronchoconstriction and shortness of breath...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28062484/heterogeneity-of-airway-dimensions-in-humans-a-critical-determinant-of-lung-function-in-asthmatics-and-non-asthmatics
#17
Christopher D Pascoe, Chun Y Seow, Tillie-Louise Hackett, Peter D Paré, Graham M Donovan
Airway remodeling, a key feature of asthma, alters every layer of the airway wall but most strikingly the airway smooth muscle (ASM) layer. Airway remodeling in asthmatics contributes to fixed airflow obstruction and can amplify airway narrowing caused by ASM activation. Previous modeling studies have shown that the increase in ASM mass has the largest effect on increasing maximal airway narrowing. Simulated heterogeneity in the dimensions and properties of the airway wall can further amplify airway narrowing...
January 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28062322/mir-23b-controls-tgf-%C3%AE-1-induced-airway-smooth-muscle-cell-proliferation-via-direct-targeting-of-smad3
#18
Ming Chen, Jianting Shi, Wei Zhang, Linjie Huang, Xiaoling Lin, Zhiqiang Lv, Wei Zhang, Ruiyun Liang, Shanping Jiang
BACKGROUND: MicroRNAs are small yet versatile gene tuners that regulate a variety of cellular processes, including cell growth and proliferation. Here we report that miR-23b inhibited airway smooth muscle cells (ASMCs) proliferation through directly targeting of Smad3. METHODS: We obtained ASMCs by laser capture microdissection of normal and asthmatic mice lung tissues. Mice ASMCs were cultured and induced by TGF-β1. The implication between TGF-β1 and miR-23b in ASMCs were detected by RT-PCR...
January 3, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28056993/effect-of-active-vitamin-d3-on-vegf-induced-adam33-expression-and-proliferation-in-human-airway-smooth-muscle-cells-implications-for-asthma-treatment
#19
Sung-Ho Kim, Qing-Mei Pei, Ping Jiang, Min Yang, Xue-Jiao Qian, Jiang-Bo Liu
BACKGROUND: Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodeling, which is associated with increased airway smooth muscle (ASM) mass. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodeling in asthma. Recent evidence indicates that a deficiency of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) may influence asthma pathogenesis. A disintegrin and metalloproteinase (ADAM)33 has been identified as playing a role in the pathophysiology of asthma...
January 5, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28042341/anti-angiogenic-nanotherapy-inhibits-airway-remodeling-and-hyper-responsiveness-of-dust-mite-triggered-asthma-in-the-brown-norway-rat
#20
Gregory M Lanza, John Jenkins, Anne H Schmieder, Aigul Moldobaeva, Grace Cui, Huiying Zhang, Xiaoxia Yang, Qiong Zhong, Jochen Keupp, Ismail Sergin, Krishna S Paranandi, Lindsey Eldridge, John S Allen, Todd Williams, Michael J Scott, Babak Razani, Elizabeth M Wagner
Although angiogenesis is a hallmark feature of asthmatic inflammatory responses, therapeutic anti-angiogenesis interventions have received little attention. Objective: Assess the effectiveness of anti-angiogenic Sn2 lipase-labile prodrugs delivered via αvβ3-micellar nanotherapy to suppress microvascular expansion, bronchial remodeling, and airway hyper-responsiveness in Brown Norway rats exposed to serial house dust mite (HDM) inhalation challenges. Results: Anti-neovascular effectiveness of αvβ3-mixed micelles incorporating docetaxel-prodrug (Dxtl-PD) or fumagillin-prodrug (Fum-PD) were shown to robustly suppress neovascular expansion (p<0...
2017: Theranostics
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