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Asthma AND gene expression

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https://www.readbyqxmd.com/read/28528200/sputum-transcriptomics-reveal-up-regulation-of-il-1-receptor-family-members-in-severe-asthma
#1
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/28527151/association-of-the-mir-196a2-mir-146a-and-mir-499-polymorphisms-with-asthma-phenotypes-in-a-korean-population
#2
Hoang Kim Tu Trinh, Duy Le Pham, Su-Chin Kim, Ri-Yeon Kim, Hae-Sim Park, Seung-Hyun Kim
BACKGROUND: MicroRNAs (miRNAs) modulate expressions of inflammatory genes, thereby regulating inflammatory responses. Single nucleotide polymorphisms (SNPs) in miRNAs could affect their efficiency in binding to messenger RNAs (mRNAs). OBJECTIVE: We investigated the associations of miRNA SNPs with asthma phenotypes. miR-196a2 (rs11614913 T>C), miR-146a (rs2910164 C>G), and miR-499 (rs3746444 A>G) were genotyped in 347 asthma patients and 172 normal healthy controls (NCs)...
May 19, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28526682/aeroallergens-induce-reactive-oxygen-species-production-and-dna-damage-and-dampen-antioxidant-responses-in-bronchial-epithelial-cells
#3
Tze Khee Chan, W S Daniel Tan, Hong Yong Peh, W S Fred Wong
Exposure to environmental allergens is a major risk factor for asthma development. Allergens possess proteolytic activity that is capable of disrupting the airway epithelium. Although there is increasing evidence pointing to asthma as an epithelial disease, the underlying mechanism that drives asthma has not been fully elucidated. In this study, we investigated the direct DNA damage potential of aeroallergens on human bronchial epithelial cells and elucidated the mechanisms mediating the damage. Human bronchial epithelial cells, BEAS-2B, directly exposed to house dust mites (HDM) resulted in enhanced DNA damage, as measured by the CometChip and the staining of DNA double-strand break marker, γH2AX...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28515280/airway-epithelial-cells-are-crucial-targets-of-glucocorticoids-in-a-mouse-model-of-allergic-asthma
#4
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
#5
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/28510638/%C3%AE-asarone-suppresses-the-proliferation-and-migration-of-asmcs-through-targeting-the-lncrna-pvt1-mir-203a-e2f3-signal-pathway-in-rsv-infected-rats
#6
Xiao Yu, Zhe Zhe, Binqing Tang, Shaobin Li, Ling Tang, Yingen Wu, Xiaorong Chen, Hong Fang
Asthma is a chronic inflammatory pulmonary disease and respiratory syncytial virus (RSV) infection is a common cause of lower respiratory tract illness in infants and young children. α-Asarone presents many pharmacological effects and has been demonstrated to be useful in treating asthma. However, the functional mechanism of α-asarone in RSV-infected asthma has not been investigated. Long non-coding RNAs (lncRNAs) have been reported to play critical roles in many biological processes. Although many lncRNAs have been characterized, few were reported in asthma, especially in RSV-induced asthma...
May 16, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28493984/nasal-airway-epithelial-cell-il-6-and-fkbp51-gene-expression-and-steroid-sensitivity-in-asthmatic-children
#7
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/28488322/impact-of-the-genetic-variants-of-glcci1-on-clinical-features-of-asthmatic-patients
#8
Shinji Chiba, Yutaka Nakamura, Tomoki Mizuno, Kazuyuki Abe, Yosuke Horii, Hiromi Nagashima, Nobuhito Sasaki, Hiroyuki Kanno, Tatsuo Tanita, Kohei Yamauchi
Background Several gene variants are associated with a response to an inhaled corticosteroids (ICSs) treatment in patients with bronchial asthma. A variant of the glucocorticoid-induced transcript 1 (GLCCI1) genes has previously been associated with decreased lung function improvement upon treatment with inhaled corticosteroids in patients with bronchial asthma. Another report has also demonstrated that this genetic biomarker did not influence the change in flow volume in one second. However, no studies have considered the treatment content and the GLCCI1 variants...
May 9, 2017: Clinical Respiratory Journal
https://www.readbyqxmd.com/read/28481620/ifn%C3%AE-influences-epithelial-anti-viral-responses-via-histone-methylation-of-the-rig-i-promoter
#9
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
#10
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/28474507/il-17f-induces-il-6-via-tak1-nf%C3%AE%C2%BAb-pathway-in-airway-smooth-muscle-cells
#11
Masayuki Nakajima, Mio Kawaguchi, Kyoko Ota, Junichi Fujita, Satoshi Matsukura, Shau-Ku Huang, Yuko Morishima, Yukio Ishii, Hiroaki Satoh, Tohru Sakamoto, Nobuyuki Hizawa
INTRODUCTION: Interleukin (IL)-17F plays a critical role in the pathophysiology of asthma. However, the precise role of IL-17F in airway smooth muscle cells (ASMCs) and its regulatory mechanisms remain to be defined. Therefore, we sought to investigate the expression of IL-6 by IL-17F and the involvement of transforming growth factor β-activated kinase 1 (TAK1) and nuclear factor (NF)-κB by in ASMCs. METHODS: ASMCs were cultured in the presence or absence of IL-17F...
June 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28473323/gabaa-receptor-%C3%AE-4-subunit-knockout-enhances-lung-inflammation-and-airway-reactivity-in-a-murine-asthma-model
#12
Gene T Yocum, Damian L Turner, Jennifer Danielsson, Matthew B Barajas, Yi Zhang, Dingbang Xu, Neil Harrison, Gregg E Homanics, Donna L Farber, Charles W Emala
Emerging evidence indicates that hypnotic anesthetics affect immune function. Many anesthetics potentiate γ-aminobutyric acid A receptor (GABAAR) activation, and these receptors are expressed on multiple subtypes of immune cells, providing a potential mechanistic link. Like immune cells, airway smooth muscle (ASM) cells also express GABAARs, particularly isoforms containing α4 subunits, and activation of these receptors leads to ASM relaxation. We sought to determine if GABAAR signaling modulates the ASM contractile and inflammatory phenotype of a murine allergic asthma model utilizing GABAAR α4 subunit global knockout (KO; Gabra4(0/0)) mice...
May 4, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28463995/neuropeptide-s-nps-variants-modify-the-signaling-and-risk-effects-of-nps-receptor-1-npsr1-variants-in-asthma
#13
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
#14
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/28458159/celastrol-reduces-il-1%C3%AE-induced-matrix-catabolism-oxidative-stress-and-inflammation-in-human-nucleus-pulposus-cells-and-attenuates-rat-intervertebral-disc-degeneration-in-vivo
#15
Jian Chen, Jun Xuan, Yun-Tao Gu, Ke-Si Shi, Jun-Jun Xie, Jiao-Xiang Chen, Zeng-Ming Zheng, Yu Chen, Xi-Bang Chen, Yao-Sen Wu, Xiao-Lei Zhang, Xiang-Yang Wang
Celastrol has been reported to exert therapeutic potential on pro-inflammatory diseases including asthma, Crohn's disease, arthritis and neurodegenerative disorders via inhibiting NF-κB pathway. While the effect of celastrol on intervertebral disc degeneration (IDD), which is also a pro-inflammatory disease, remains unknown. In this study, we evaluated the effect of celastrol on IDD in IL-1β treated human nucleus pulposus cells in vitro as well as in puncture induced rat IDD model in vivo. Our results showed that celastrol reduced the expression of catabolic genes (MMP-3, 9, 13, ADAMTS-4, 5), oxidative stress factors (COX-2, iNOS) and pro-inflammatory factors (IL-6, TNF-a) induced by IL-1β in nucleus pulposus cells, also phosphorylation of IκBα and p65 were attenuated by celastrol, indicating NF-κB pathway was inhibited by celastrol in nucleus pulposus cells...
April 27, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28440659/alleviation-of-multiple-asthmatic-pathologic-features-with-orally-available-and-subtype-selective-gabaa-receptor-modulators
#16
Gloria S Forkuo, Amanda N Nieman, Nina Y Yuan, Revathi Kodali, Olivia B Yu, Nicolas M Zahn, Rajwana Jahan, Guanguan Li, Michael Rajesh Stephen, Margaret L Guthrie, Michael M Poe, Benjamin D Hartzler, Ted W Harris, Gene T Yocum, Charles W Emala, Douglas A Steeber, Douglas C Stafford, James M Cook, Leggy A Arnold
We describe pharmacokinetic and pharmacodynamic properties of two novel oral drug candidates for asthma. Phenolic α4β3γ2 GABAAR selective compound 1 and acidic α5β3γ2 selective GABAAR positive allosteric modulator compound 2 relaxed airway smooth muscle ex vivo and attenuated airway hyperresponsiveness (AHR) in a murine model of asthma. Importantly, compound 2 relaxed acetylcholine contracted human tracheal airway smooth muscle strips. Oral treatment of compounds 1 and 2 decreased eosinophils in bronchoalveolar lavage fluid in ovalbumin sensitized and challenged mice, thus exhibiting anti-inflammatory properties...
May 1, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28431562/effects-of-the-common-polymorphism-in-the-human-aldehyde-dehydrogenase-2-aldh2-gene-on-the-lung
#17
Aoi Kuroda, Ahmed E Hegab, Gao Jingtao, Shuji Yamashita, Nobuyuki Hizawa, Tohru Sakamoto, Hideyasu Yamada, Satoshi Suzuki, Makoto Ishii, Ho Namkoong, Takanori Asakura, Mari Ozaki, Hiroyuki Yasuda, Junko Hamamoto, Shizuko Kagawa, Kenzo Soejima, Tomoko Betsuyaku
BACKGROUND: Aldehyde dehydrogenases (ALDHs) play a major role in detoxification of aldehydes. High expression of ALDHs is a marker for stem cells of many organs including the lungs. A common polymorphism in ALDH2 gene (ALDH2*2) results in inactivation of the enzyme and is associated with alcohol flushing syndrome and increased risk for cardiovascular and Alzheimer's diseases and some cancers. The effect of this ALDH2 polymorphism on the lung and its stem cells has not been thoroughly examined...
April 21, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28424691/increased-autophagy-related-5-gene-expression-is-associated-with-collagen-expression-in-the-airways-of-refractory-asthmatics
#18
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/28420758/the-foxm1-inhibitor-rcm-1-suppresses-goblet-cell-metaplasia-and-prevents-il-13-and-stat6-signaling-in-allergen-exposed-mice
#19
Lifeng Sun, Xiaomeng Ren, I-Ching Wang, Arun Pradhan, Yufang Zhang, Hannah M Flood, Bo Han, Jeffrey A Whitsett, Tanya V Kalin, Vladimir V Kalinichenko
Goblet cell metaplasia and excessive mucus secretion associated with asthma, cystic fibrosis, and chronic obstructive pulmonary disease contribute to morbidity and mortality worldwide. We performed a high-throughput screen to identify small molecules targeting a transcriptional network critical for the differentiation of goblet cells in response to allergens. We identified RCM-1, a nontoxic small molecule that inhibited goblet cell metaplasia and excessive mucus production in mice after exposure to allergens...
April 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28415826/azithromycin-augments-rhinovirus-induced-ifn%C3%AE-via-cytosolic-mda5-in-experimental-models-of-asthma-exacerbation
#20
Mandy Menzel, Hamid Akbarshahi, Ellen Tufvesson, Carl Persson, Leif Bjermer, Lena Uller
Deficient production of anti-viral interferons (IFNs) may be involved in causing viral-induced asthma exacerbations. Hence, drugs inducing lung IFN production would be warranted. Azithromycin may reduce asthma exacerbations but its modus operandi is unknown. Here, we investigated if azithromycin induces IFNβ expression in vitro in rhinovirus-infected bronchial epithelial cells from asthmatic donors and in vivo in our allergic inflammation-based mouse model of viral stimulus-induced asthma exacerbations. Azithromycin dose-dependently augmented viral-induced IFNβ expression in asthmatic, but not in healthy bronchial epithelial cells...
May 9, 2017: Oncotarget
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