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Asthma AND "gene expression"

Ivana V Yang, Brent S Pedersen, Andrew H Liu, George T O'Connor, Dinesh Pillai, Meyer Kattan, Rana Tawil Misiak, Rebecca Gruchalla, Stanley J Szefler, Gurjit K Khurana Hershey, Carolyn Kercsmar, Adam Richards, Allen D Stevens, Christena A Kolakowski, Melanie Makhija, Christine A Sorkness, Rebecca Z Krouse, Cynthia Visness, Elizabeth J Davidson, Corinne E Hennessy, Richard J Martin, Alkis Togias, William W Busse, David A Schwartz
BACKGROUND: Given the strong environmental influence on both epigenetic marks and allergic asthma in children, the epigenetic alterations in respiratory epithelia might provide insight into allergic asthma. OBJECTIVE: We sought to identify DNA methylation and gene expression changes associated with childhood allergic persistent asthma. METHODS: We compared genomic DNA methylation patterns and gene expression in African American children with persistent atopic asthma (n = 36) versus healthy control subjects (n = 36)...
October 13, 2016: Journal of Allergy and Clinical Immunology
Kristi J Warren, Xi Fang, Nagaraj M Gowda, Joshua J Thompson, Nicola M Heller
Lung M2 macrophages are regulators of airway inflammation, associated with poor lung function in allergic asthma. Previously, we demonstrated that IL-4-induced M2 gene expression correlated with tyrosine phosphorylation of the insulin receptor substrate (IRS)-2 in macrophages. We hypothesized that negative regulation of IRS-2 activity following IL-4 stimulation is dependent upon serine phosphorylation of IRS-2. Herein, we describe an inverse relationship between tyrosine phosphorylation (pY) and serine phosphorylation (pS) of IRS-2 following IL-4 stimulation...
October 14, 2016: Journal of Biological Chemistry
Mark Bazett, Agnieszka Biala, Ryan D Huff, Momir Bosiljcic, Hal Gunn, Shirin Kalyan, Jeremy A Hirota
There is an unmet need for effective new and innovative treatments for asthma. It is becoming increasingly evident that bacterial stimulation can have beneficial effects at attenuating allergic airway disease through immune modulation. Our aim was to test the ability of a novel inactivated microbe-derived therapeutic based on Klebsiella (KB) in a model of allergic airway disease in mice. BALB/c mice were exposed intranasally to house dust mite (HDM) for two weeks. Mice were treated prophylactically via subcutaneous route with either KB or placebo for one week prior to HDM exposure and throughout the two week exposure period...
October 13, 2016: Scientific Reports
Diamanda Rigas, Gavin Lewis, Jennifer L Aron, Bowen Wang, Homayon Banie, Ishwarya Sankaranarayanan, Lauriane Galle-Treger, Hadi Maazi, Richard Lo, Gordon J Freeman, Arlene H Sharpe, Pejman Soroosh, Omid Akbari
BACKGROUND: Atopic diseases including asthma exacerbate type 2 immune responses and involve a number of immune cell types, including regulatory T cells (Tregs) and the emerging group 2 innate lymphoid cells (ILC2s). While ILC2s are potent producers of type 2 cytokines, the regulation of ILC2 activation and function is not well understood. OBJECTIVE: In the present study, we evaluate for the first time how Tregs interact with pulmonary ILC2s and control their function...
October 4, 2016: Journal of Allergy and Clinical Immunology
Amal Al-Garawi, Vincent J Carey, Divya Chhabra, Hooman Mirzakhani, Jarrett Morrow, Jessica Lasky-Su, Weiliang Qiu, Nancy Laranjo, Augusto A Litonjua, Scott T Weiss
BACKGROUND: Patterns of gene expression of human pregnancy are poorly understood. In a trial of vitamin D supplementation in pregnant women, peripheral blood transcriptomes were measured longitudinally on 30 women and used to characterize gene co-expression networks. OBJECTIVE: Studies suggest that increased maternal Vitamin D levels may reduce the risk of asthma in early life, yet the underlying mechanisms have not been examined. In this study, we used a network-based approach to examine changes in gene expression profiles during the course of normal pregnancy and evaluated their association with maternal Vitamin D levels...
2016: PloS One
M A E Nieuwenhuis, J M Vonk, B E Himes, C Sarnowski, C Minelli, D Jarvis, E Bouzigon, D C Nickle, M Laviolette, D Sin, S T Weiss, M van den Berge, G H Koppelman, D S Postma
BACKGROUND: The severity of bronchial hyperresponsiveness (BHR) is a fundamental feature of asthma. The severity of BHR varies between asthmatics and is associated with lack of asthma control. The mechanisms underlying this trait are still unclear. This study aims to identify genes associated with BHR severity, using a genome wide association study (GWAS) on the slope of BHR in adult asthmatics. METHODS: We performed a GWAS on BHR severity in adult asthmatics from the Dutch Asthma GWAS cohort (n=650), adjusting for smoking and inhaled corticosteroid use, and verified results in 3 other cohorts...
October 6, 2016: Allergy
Nicola L D Overton, David W Denning, Paul Bowyer, Angela Simpson
BACKGROUND: In patients with asthma, the fungus Aspergillus fumigatus can cause allergic bronchopulmonary aspergillosis (ABPA). Familial ABPA is reported, and some genetic factors have been associated with the disease, however, these are small studies (n ≤ 38) and do not explain all cases of ABPA. METHODS: We analysed SNPs in 95 ABPA patients, comparing frequencies to 152 atopic asthmatic and 279 healthy controls. Twenty two genes were selected from literature, and 195 tagging SNPs were analysed for genetic association with ABPA using logistic regression corrected for multiple testing...
2016: Allergy, Asthma, and Clinical Immunology
Reena Berman, Di Jiang, Qun Wu, Connor R Stevenson, Niccolette R Schaefer, Hong Wei Chu
BACKGROUND: MUC18 is upregulated in the lungs of asthma and COPD patients. It has been shown to have pro-inflammatory functions in cultured human airway epithelial cells during viral infections and in mice during lung bacterial infections. However, the in vivo role of MUC18 in the context of viral infections remains poorly understood. The goal of this study is to define the in vivo function of MUC18 during respiratory rhinovirus infection. METHODS: Muc18 wild-type (WT) and knockout (KO) mice were infected with human rhinovirus 1B (HRV-1B) and sacrificed after 1 day to determine the inflammatory and antiviral responses...
2016: PloS One
Grissel Faura Tellez, Brigitte W M Willemse, Uilke Brouwer, Susan Nijboer-Brinksma, Karl Vandepoele, Jacobien A Noordhoek, Irene Heijink, Maaike de Vries, Natalie P Smithers, Dirkje S Postma, Wim Timens, Laura Wiffen, Frans van Roy, John W Holloway, Peter M Lackie, Martijn C Nawijn, Gerard H Koppelman
BACKGROUND: The asthma gene PCDH1 encodes Protocadherin-1, a putative adhesion molecule of unknown function expressed in the airway epithelium. Here, we characterize the localization, differential expression, homotypic adhesion specificity and function of PCDH1 in airway epithelial cells in asthma. METHODS: We performed confocal fluorescence microscopy to determine subcellular localization of PCDH1 in 16HBE cells and primary bronchial epithelial cells (PBECs) grown at air-liquid interface...
2016: PloS One
Mingyuan Han, Jun Young Hong, Suraj Jaipalli, Charu Rajput, Jing Lei, Joanna L Hinde, Qiang Chen, Natalie M Hershenson, J Kelley Bentley, Marc B Hershenson
Early-life wheezing-associated infections with rhinovirus (RV) have been associated with asthma development in children. We have shown that RV infection of six day-old mice induces mucous metaplasia and airways hyperresponsiveness which is dependent on IL-13, IL-25 and type 2 innate lymphoid cells (ILC2s). Infection of immature mice fails to induce lung IFN-γ expression, in contrast to mature 8 week-old mice with a robust IFN-γ response, consistent with the notion that deficient IFN-γ production in immature mice permits RV-induced type 2 immune responses...
September 28, 2016: American Journal of Respiratory Cell and Molecular Biology
Marcelina Koćwin, Mateusz Jonakowski, Marcelina Przemęcka, Jan Zioło, Michał Panek, Piotr Kuna
Asthma is a chronic inflammatory heterogeneous disease of the lower respiratory tract characterised by the occurrence of bronchial hyper-responsiveness and paroxysmal, changeable bronchial obstruction. Transforming growth factor-beta (TGF-b) is one of the cytokines involved in mediating airway inflammation and remodelling. The level of TGF-b1 gene expression correlates with severity of symptoms. Alterations in the main SMAD signal transmission, overexpression of TGF-b genes and changes in the transcriptome cause excessive secretion of TGF-b and its increased expression in target cells, which clinically induces a moderate-severe or severe course of asthma as well as an earlier and faster disease progression...
2016: Pneumonologia i Alergologia Polska
Jean A Hall, Jaye Hartman, Monica M Skinner, Adam R Schwindt, Kay A Fischer, William R Vorachek, Gerd Bobe, Beth A Valentine
The prevalence of asthma has increased in recent decades, which may be related to higher dietary intake of (n-6) polyunsaturated fatty acids (PUFA) and lower intake of (n-3) PUFA, e.g., those contained in fish oil. The objective of this study was to determine if dietary PUFA enrichment decreases mucus production or the inflammatory response associated with ovalbumin (OVA)-induced allergic lung inflammation. Mice (n = 10/group) were fed control, 20% fish oil, or 20% corn oil enriched diets for a total of 12 weeks...
2016: PloS One
Anne M Fitzpatrick, Susan T Stephenson, Milton R Brown, Khristopher Nguyen, Shaneka Douglas, Lou Ann S Brown
BACKGROUND: Severe asthma in children is a heterogeneous disorder associated with variable responses to corticosteroid treatment. Criterion standards for corticosteroid responsiveness assessment in children are lacking. OBJECTIVE: This study sought to characterize systemic corticosteroid responses in children with severe asthma after treatment with intramuscular triamcinolone and to identify phenotypic and molecular predictors of an intramuscular triamcinolone response...
September 21, 2016: Journal of Allergy and Clinical Immunology in Practice
Robert Newton, Mark A Giembycz
In moderate-to-severe asthma, adding-on an inhaled long-acting β2 -adenoceptor agonist (LABA) to an inhaled corticosteroid (ICS) provides superior disease control than simply increasing the dose of ICS. Acting on the glucocorticoid receptor (GR, gene NR3C1), ICSs promote anti-inflammatory/anti-asthma gene expression. In vitro, LABAs synergistically enhance the maximal expression of many glucocorticoid-induced genes. Other genes, including DUSP1 in human airways smooth muscle (ASM) and epithelial cells, are up-regulated additively by both drug classes...
September 20, 2016: British Journal of Pharmacology
Maria J Gutierrez, Jose L Gomez, Geovanny F Perez, Krishna Pancham, Stephanie Val, Dinesh K Pillai, Mamta Giri, Sarah Ferrante, Robert Freishtat, Mary C Rose, Diego Preciado, Gustavo Nino
BACKGROUND: Innate immune responses are fine-tuned by small noncoding RNA molecules termed microRNAs (miRs) that modify gene expression in response to the environment. During acute infections, miRs can be secreted in extracellular vesicles (EV) to facilitate cell-to-cell genetic communication. The purpose of this study was to characterize the baseline population of miRs secreted in EVs in the airways of young children (airway secretory microRNAome) and examine the changes during rhinovirus (RV) infection, the most common cause of asthma exacerbations and the most important early risk factor for the development of asthma beyond childhood...
2016: PloS One
Shamila D Alipoor, Ian M Adcock, Johan Garssen, Esmaeil Mortaz, Mohammad Varahram, Mehdi Mirsaeidi, Aliakbar Velayati
MicroRNAs (miRNAs) are small non-coding RNAs which can act as master regulators of gene expression, modulate almost all biological process and are essential for maintaining cellular homeostasis. Dysregulation of miRNA expression has been associated with aberrant gene expression and may lead to pathological conditions. Evidence suggests that miRNA expression profiles are altered between health and disease and as such may be considered as biomarkers of disease. Evidence is increasing that miRNAs are particularly important in lung homeostasis and development and have been demonstrated to be the involved in many pulmonary diseases such as asthma, COPD, sarcoidosis, lung cancer and other smoking related diseases...
September 12, 2016: European Journal of Pharmacology
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
Hyeon-Jong Yang
Allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food allergy, are most common chronic, noncommunicable diseases in childhood. In the past few decades, the prevalence has increased abruptly worldwide. There are 2 possible explanations for the rising prevalence of allergic diseases worldwide, that an increased disease-awareness of physician, patient, or caregivers, and an abrupt exposure to unknown hazards. Unfortunately, the underlying mechanisms remain largely unknown. Despite the continuing efforts worldwide, the etiologies and rising prevalence remain unclear...
August 2016: Korean Journal of Pediatrics
Jos L J van der Velden, Ying Ye, James D Nolin, Sidra M Hoffman, David G Chapman, Karolyn G Lahue, Sarah Abdalla, Peng Chen, Yong Liu, Brydon Bennett, Nasreen Khalil, Donna Sutherland, William Smith, Gerald Horan, Mahmoud Assaf, Zebulun Horowitz, Rajesh Chopra, Randall M Stevens, Maria Palmisano, Yvonne M W Janssen-Heininger, Peter H Schafer
BACKGROUND: Lung remodeling and pulmonary fibrosis are serious, life-threatening conditions resulting from diseases such as chronic severe asthma and idiopathic pulmonary fibrosis (IPF). Preclinical evidence suggests that JNK enzyme function is required for key steps in the pulmonary fibrotic process. However, a selective JNK inhibitor has not been investigated in translational models of lung fibrosis with clinically relevant biomarkers, or in IPF patients. METHODS: The JNK inhibitor CC-930 was evaluated in the house dust mite-induced fibrotic airway mouse model, in a phase I healthy volunteer pharmacodynamic study, and subsequently in a phase II multicenter study of mild/moderate IPF (n = 28), with a 4-week, placebo-controlled, double-blind, sequential ascending-dose period (50 mg QD, 100 mg QD, 100 mg BID) and a 52-week open-label treatment-extension period...
December 2016: Clinical and Translational Medicine
Chih-Hsi Scott Kuo, Stelios Pavlidis, Matthew Loza, Fred Baribaud, Anthony Rowe, Ioannis Pandis, Uruj Hoda, Christos Rossios, Ana Sousa, Susan J Wilson, Peter Howarth, Barbro Dahlen, Sven-Erik Dahlen, Pascal Chanez, Dominick Shaw, Norbert Krug, Thomas Sandström, Bertrand De Meulder, Diane Lefaudeux, Stephen Fowler, Louise Fleming, Julie Corfield, Charles Auffray, Peter J Sterk, Ratko Djukanovic, Yike Guo, Ian M Adcock, Kian Fan Chung
RATIONALE AND OBJECTIVES: Asthma is a heterogeneous disease driven by diverse immunologic and inflammatory mechanisms. We used transcriptomic profiling of airway tissues to help define asthma phenotypes. METHODS: The transcriptome from bronchial biopsies and epithelial brushings of 107 moderate-to-severe asthmatics were annotated by gene-set variation analysis (GSVA) using 42 gene-signatures relevant to asthma, inflammation and immune function. Topological data analysis (TDA) of clinical and histological data was used to derive clusters and the nearest shrunken centroid algorithm used for signature refinement...
August 31, 2016: American Journal of Respiratory and Critical Care Medicine
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