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Asthma AND "gene expression"

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https://www.readbyqxmd.com/read/28529457/deguelin-attenuates-allergic-airway-inflammation-via-inhibition-of-nf-%C3%AE%C2%BAb-pathway-in-mice
#1
Zhang Bao, Pei Zhang, Yinan Yao, Guohua Lu, Zhongkai Tong, Bing Yan, Lingfang Tu, Guangdie Yang, Jianying Zhou
Asthma is a chronic respiratory disease characterized by airway inflammation and remodeling, resulting in a substantial economic burden on both patients and society. Deguelin, a constituent of the Leguminosae family, exhibits anti-proliferative and anti-inflammatory activities in cancer mice models via inhibiting phosphatidylinositol 3-kinases and the NF-κB pathway. We demonstrated that deguelin effectively reduced OVA-induced inflammatory cell recruitment, decreased lung tissue inflammation and mucus production, suppressed airway hyperresponsiveness, and inhibited serum immunoglobulin and Th2 cytokine levels in a dose-dependent manner in asthmatic mice...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28528200/sputum-transcriptomics-reveal-up-regulation-of-il-1-receptor-family-members-in-severe-asthma
#2
Christos Rossios, Stelios Pavlidis, Uruj Hoda, Chih-Hsi Kuo, Coen Wiegman, Kirsty Russell, Kai Sun, Matthew J Loza, Frederic Baribaud, Andrew L Durham, Oluwaseun Ojo, Rene Lutter, Anthony Rowe, Aruna Bansal, Charles Auffray, Ana Sousa, Julie Corfield, Ratko Djukanovic, Yike Guo, Peter J Sterk, Kian Fan Chung, Ian M Adcock
BACKGROUND: Sputum analysis in asthma is used to define airway inflammatory processes and may guide therapy. OBJECTIVE: To determine differential gene and protein expression in sputum samples from patients with severe asthma (SA) compared to mild-moderate non-smoking asthmatics (MMA). METHODS: Induced sputum was obtained from non-smoking SA (SAn), smokers/ex-smokers with SA (SAsm), MMA and healthy non-smoking controls. Differential cell counts, microarray analysis of cell pellets and SOMAscan analysis of sputum analytes was performed...
May 17, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28515280/airway-epithelial-cells-are-crucial-targets-of-glucocorticoids-in-a-mouse-model-of-allergic-asthma
#3
Carina Klaßen, Anna Karabinskaya, Lien Dejager, Sabine Vettorazzi, Justine Van Moorleghem, Fred Lühder, Sebastiaan H Meijsing, Jan P Tuckermann, Hanibal Bohnenberger, Claude Libert, Holger M Reichardt
Although glucocorticoids (GCs) are a mainstay in the clinical management of asthma, the target cells that mediate their therapeutic effects are unknown. Contrary to our expectation, we found that GC receptor (GR) expression in immune cells was dispensable for successful therapy of allergic airway inflammation (AAI) with dexamethasone. Instead, GC treatment was compromised in mice expressing a defective GR in the nonhematopoietic compartment or selectively lacking the GR in airway epithelial cells. Further, we found that an intact GR dimerization interface was a prerequisite for the suppression of AAI and airway hyperresponsiveness by GCs...
May 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28513859/identification-of-a-plasma-mirna-biomarker-signature-for-allergic-asthma-a-translational-approach
#4
Katrin Milger, Jeremias Götschke, Linda Krause, Petra Nathan, Francesca Alessandrini, Amanda Tufman, Rainald Fischer, Sabine Bartel, Fabian J Theis, Jürgen Behr, Stefan Dehmel, Nikola S Mueller, Nikolaus Kneidinger, Susanne Krauss-Etschmann
BACKGROUND: Asthma is a heterogeneous chronic disease with different phenotypes and treatment responses. Thus, there is a high clinical need for molecular disease biomarkers to aid in differentiating these distinct phenotypes. As MicroRNAs (miRNAs), that regulate gene expression at the post-transcriptional level, are altered in experimental and human asthma, circulating miRNAs are attractive candidates for the identification of novel biomarkers. This study aimed to identify plasmatic miRNA-based biomarkers of asthma, through a translational approach...
May 17, 2017: Allergy
https://www.readbyqxmd.com/read/28493984/nasal-airway-epithelial-cell-il-6-and-fkbp51-gene-expression-and-steroid-sensitivity-in-asthmatic-children
#5
Michael Fayon, Aurelie Lacoste-Rodrigues, Pascal Barat, Jean-Christophe Helbling, Fabienne Nacka, Patrick Berger, Marie-Pierre Moisan, Jean-Benoit Corcuff
BACKGROUND: Many asthmatic patients exhibit uncontrolled asthma despite high-dose inhaled corticosteroids (ICS). Airway epithelial cells (AEC) have distinct activation profiles that can influence ICS response. OBJECTIVES: A pilot study to identify gene expression markers of AEC dysfunction and markers of corticosteroid sensitivity in asthmatic and non-asthmatic control children, for comparison with published reports in adults. METHODS: AEC were obtained by nasal brushings and primary submerged cultures, and incubated in control conditions or in the presence of 10 ng/ml TNFalpha, 10-8M dexamethasone, or both...
2017: PloS One
https://www.readbyqxmd.com/read/28481620/ifn%C3%AE-influences-epithelial-anti-viral-responses-via-histone-methylation-of-the-rig-i-promoter
#6
C Mirella Spalluto, Akul Singhania, Doriana Cellura, Christopher H Woelk, Tilman Sanchez-Elsner, Karl J Staples, Tom M A Wilkinson
The asthmatic lung is prone to respiratory viral infections that exacerbate the symptoms of the underlying disease. Recent work has suggested that a deficient Th1 response in early life may lead to these aberrant anti-viral responses. We investigated whether the inflammatory environment of the airway epithelium could modulate anti-viral gene expression via epigenetic mechanisms, in order to study the development of a long-term dysregulation of innate responses, which are a hallmark of asthma. We primed AALEB, a human bronchial epithelial cell line, with IFNγ and IL13 and subsequently infected cells with Respiratory Syncytial Virus (RSV) and innate anti-viral genes expression and their epigenetic markers were analysed...
May 8, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28479334/cdc42-related-genes-are-upregulated-in-helper-t-cells-from-obese-asthmatic-children
#7
Deepa Rastogi, John Nico, Andrew D Johnston, Toni Adrianne M Tobias, Yurydia Jorge, Fernando Macian, John M Greally DMed
BACKGROUND: Pediatric obesity-related asthma is more severe and less responsive to medications than asthma in normal-weight children. Obese asthmatic children have nonatopic TH1-polarized systemic inflammation that correlates with pulmonary function deficits, but the pathways underlying TH1-polarized inflammation are not well understood. OBJECTIVE: We compared the CD4(+) T-cell transcriptome in obese children with asthma with that in normal-weight children with asthma to identify key differentially expressed genes associated with TH1-polarized inflammation...
May 4, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28463995/neuropeptide-s-nps-variants-modify-the-signaling-and-risk-effects-of-nps-receptor-1-npsr1-variants-in-asthma
#8
Nathalie Acevedo, Sini Ezer, Simon Kebede Merid, Vincent D Gaertner, Cilla Söderhäll, Mauro D'Amato, Michael Kabesch, Erik Melén, Juha Kere, Ville Pulkkinen
Single nucleotide polymorphisms (SNPs) close to the gain-of-function substitution, Asn(107)Ile (rs324981, A>T), in Neuropeptide S Receptor 1 (NPSR1) have been associated with asthma. Furthermore, a functional SNP (rs4751440, G>C) in Neuropeptide S (NPS) encodes a Val(6)Leu substitution on the mature peptide that results in reduced bioactivity. We sought to examine the effects of different combinations of these NPS and NPSR1 variants on downstream signaling and genetic risk of asthma. In transfected cells, the magnitude of NPSR1-induced activation of cAMP/PKA signal transduction pathways and downstream gene expression was dependent on the combination of the NPS and NPSR1 variants with NPS-Val(6)/NPSR1-Ile(107) resulting in strongest and NPS-Leu(6)/NPSR1-Asn(107) in weakest effects, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28463537/diagnosis-of-western-red-cedar-asthma-using-a-blood-based-gene-expression-biomarker-panel
#9
Chen Xi Yang, Amrit Singh, Young Woong Kim, Edward M Conway, Christopher Carlsten, Scott J Tebbutt
Western red cedar asthma is the most common form of occupational asthma in the Pacific Northwest region of North America and is caused by a low molecular weight molecule, plicatic acid, found in western red cedar wood. In the present study, peripheral whole blood transcriptomics was used to identify biomarker panels that distinguish asthmatic individuals who are sensitive to plicatic acid from asthmatic individuals who are not sensitive to plicatic acid. These findings suggest that blood may be used as a resource to diagnose western red cedar asthma...
May 2, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28424691/increased-autophagy-related-5-gene-expression-is-associated-with-collagen-expression-in-the-airways-of-refractory-asthmatics
#10
Audrey H Poon, David F Choy, Fazila Chouiali, Rakhee K Ramakrishnan, Bassam Mahboub, Severine Audusseau, Andrea Mogas, Jeffrey M Harris, Joseph R Arron, Catherine Laprise, Qutayba Hamid
BACKGROUND: Fibrosis, particularly excessive collagen deposition, presents a challenge for treating asthmatic individuals. At present, no drugs can remove or reduce excessive collagen in asthmatic airways. Hence, the identification of pathways involved in collagen deposition would help to generate therapeutic targets to interfere with the airway remodeling process. Autophagy, a cellular degradation process, has been shown to be dysregulated in various fibrotic diseases, and genetic association studies in independent human populations have identified autophagy-related 5 (ATG5) to be associated with asthma pathogenesis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28397284/altered-fatty-acid-metabolism-and-reduced-stearoyl-coenzyme-a-desaturase-activity-in-asthma
#11
N Rodriguez-Perez, E Schiavi, R Frei, R Ferstl, P Wawrzyniak, S Smolinska, M Sokolowska, N A Sievi, M Kohler, P Schmid-Grendelmeier, D Michalovich, K D Simpson, E M Hessel, M Jutel, M Martin-Fontecha, O Palomares, C A Akdis, L O'Mahony
BACKGROUND: Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely under-explored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and non-obese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models. METHODS: Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS...
April 11, 2017: Allergy
https://www.readbyqxmd.com/read/28379462/human-metapneumovirus-infection-in-chronic-obstructive-pulmonary-disease-impact-of-glucocorticosteroids-and-interferon
#12
Keiko Kan-O, Ruben Ramirez, Martin I MacDonald, Michael Rolph, Penny A Rudd, Kirsten M Spann, Suresh Mahalingam, Philip G Bardin, Belinda J Thomas
Background.: Human metapneumovirus (hMPV) infection is implicated in exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Research into the pathogenesis of infection is restricted to animal models and information about hMPV replication and inflammatory and immune responses in human disease is limited. Methods.: Human primary bronchial epithelial cells (PBEC) from healthy, asthmatic and COPD subjects were infected with hMPV, with or without glucocorticosteroids (GCS) exposure...
April 4, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28360114/ror%C3%AE-dependent-type-2-innate-lymphoid-cells-are-required-and-sufficient-for-mucous-metaplasia-in-immature-mice
#13
Charu Rajput, Tracy X Cui, Mingyuan Han, Jing Lei, Joanna L Hinde, Qian Wu, J Kelley Bentley, Marc B Hershenson
Early-life wheezing associated respiratory tract infection by rhinovirus (RV) is considered a risk factor for asthma development. We have shown that RV infection of 6 day-old BALB/c mice, but not mature mice, induces an asthma-like phenotype which is associated with an increase in the population of type 2 innate lymphoid cells (ILC2s) and dependent on IL-13 and IL-25. We hypothesize that ILC2s are required and sufficient for development of the asthma-like phenotype in immature mice. Mice were infected with RV1B on day 6 of life and treated with vehicle or a chemical inhibitor of retinoic acid receptor-related orphan receptor (ROR)-α, SR3335 (15 mg/kg/day intraperitoneally for 7 days)...
March 30, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28341820/il-23-gene-and-protein-expression-in-childhood-asthma
#14
Soheila Alyasin, Reza Amin, Ali Fazel, Mohammad Hossein Karimi, Seyed Hesamedin Nabavizadeh, Hossein Esmaeilzadeh, Maryam Babaei
BACKGROUND: Asthma is the chronic inflammation of airways characterized by eosinophilic infiltration, mucus overproduction, airway hyper-responsiveness and airway remodeling. These changes are induced mostly by cytokines which are produced by T helper (Th) 2 cells. Recently, the role of interleukin-23 (IL-23) in the pathogenesis of adult allergic asthma has been studied. OBJECTIVE: To explore IL-23 serum levels and its expression in persistent asthma compared with healthy children younger than five years old...
March 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28328242/human-airway-epithelial-cells-direct-significant-rhinovirus-replication-in-monocytic-cells-by-enhancing-icam1-expression
#15
Xu Zhou, Lingxiang Zhu, Rosa Lizarraga, Yin Chen
Human rhinovirus (RV) is the major cause of common cold, and it also plays a significant role in asthma and asthma exacerbation. Airway epithelium is the primary site of RV infection and production. In contrast, monocytic cells (e.g. monocytes and macrophages) are believed to be non-permissive for RV replication. Instead, RV has been shown to modulate inflammatory gene expressions in these cells via a replication-independent mechanism. In the present study, RV16 (a major-group RV) replication was found to be significantly enhanced in monocytes when co-cultivated with airway epithelial cells...
March 22, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28323055/a-6-alkylsalicylate-histone-acetyltransferase-inhibitor-inhibits-histone-acetylation-and-pro-inflammatory-gene-expression-in-murine-precision-cut-lung-slices
#16
Thea van den Bosch, Niek G J Leus, Hannah Wapenaar, Alexander Boichenko, Jos Hermans, Rainer Bischoff, Hidde J Haisma, Frank J Dekker
Lysine acetylations are post-translational modifications of cellular proteins, that are crucial in the regulation of many cellular processes. Lysine acetylations on histone proteins are part of the epigenetic code regulating gene transcription and are installed by histone acetyltransferases. Observations that inflammatory lung diseases, such as asthma and chronic obstructive pulmonary disease, are characterized by increased histone acetyltransferase activity indicate that development of small molecule inhibitors for these enzymes might be a valuable approach towards new therapies for these diseases...
March 16, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28320933/activin-a-co-opts-irf4-and-ahr-signaling-to-induce-human-regulatory-t-cells-that-restrain-asthmatic-responses
#17
Sofia Tousa, Maria Semitekolou, Ioannis Morianos, Aggelos Banos, Aikaterini I Trochoutsou, Tess M Brodie, Nikolaos Poulos, Konstantinos Samitas, Maria Kapasa, Dimitris Konstantopoulos, Giannis Paraskevopoulos, Mina Gaga, Catherine M Hawrylowicz, Federica Sallusto, Georgina Xanthou
Type 1 regulatory T (Tr1) cells play a pivotal role in restraining human T-cell responses toward environmental allergens and protecting against allergic diseases. Still, the precise molecular cues that underlie their transcriptional and functional specification remain elusive. Here, we show that the cytokine activin-A instructs the generation of CD4(+) T cells that express the Tr1-cell-associated molecules IL-10, inducible T-Cell costimulator (ICOS), lymphocyte activation gene 3 protein (LAG-3), and CD49b, and exert strongly suppressive functions toward allergic responses induced by naive and in vivo-primed human T helper 2 cells...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28295446/a-recombinant-cystatin-from-ascaris-lumbricoides-attenuates-inflammation-of-dss-induced-colitis
#18
S Coronado, L Barrios, J Zakzuk, R Regino, V Ahumada, L Franco, Y Ocampo, L Caraballo
Helminthiasis may ameliorate inflammatory diseases, such as inflammatory bowel disease and asthma. Information about immunomodulators from Ascaris lumbricoides is scarce, but could be important considering the co-evolutionary relationships between helminths and humans. We evaluated the immunomodulatory effects of a recombinant cystatin from A. lumbricoides on an acute model of dextran sodium sulphate (DSS)-induced colitis in mice. From an A. lumbricoides cDNA library, we obtained a recombinant cystatin (rAl-CPI)...
April 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28293931/investigation-of-the-possible-role-of-the-hippo-yap1-pathway-in-asthma-and-allergy
#19
Lili E Fodor, András Gézsi, Ldikó Ungvári, Agnes F Semsei, Zsófia Gál, Adrienne Nagy, Gabriella Gálffy, Lilla Tamási, András Kiss, Péter Antal, Csaba Szalai
PURPOSE: Several lines of evidence indicate that the Hippo/Yes-associated protein 1 (YAP1) pathways might play a role in the pathogenesis of asthma. To investigate the possible role of the Hippo/YAP1 pathway in the pathogenesis of asthma or its phenotypes. METHODS: The levels of gene expressions of the members of the Hippo/YAP1 were compared. The presence of the proteins of the YAP1 and FRMD6 were analyzed with Western blot in induced sputum of 18 asthmatic subjects and 10 control subjects...
May 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/28275137/a-ceacam6-high-airway-neutrophil-phenotype-and-ceacam6-high-epithelial-cells-are-features-of-severe-asthma
#20
Aarti Shikotra, David F Choy, Salman Siddiqui, Greer Arthur, Deepti R Nagarkar, Guiquan Jia, Adam K A Wright, Chandra M Ohri, Emma Doran, Claire A Butler, Beverley Hargadon, Alexander R Abbas, Janet Jackman, Lawren C Wu, Liam G Heaney, Joseph R Arron, Peter Bradding
Severe asthma represents a major unmet clinical need; understanding the pathophysiology is essential for the development of new therapies. Using microarray analysis, we previously found three immunological clusters in asthma: Th2-high, Th17-high, and Th2/17-low. Although new therapies are emerging for Th2-high disease, identifying molecular pathways in Th2-low disease remains an important goal. Further interrogation of our previously described microarray dataset revealed upregulation of gene expression for carcinoembryonic Ag cell adhesion molecule (CEACAM) family members in the bronchi of patients with severe asthma...
March 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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