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Asthma AND "gene expression"

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https://www.readbyqxmd.com/read/28649804/fibroblast-derived-exosomes-promote-epithelial-cell-proliferation-through-tgf-%C3%AE-2-signaling-pathway-in-severe-asthma
#1
Ikhlass Haj-Salem, Sophie Plante, Abdelilah S Gounni, Mahmoud Rouabhia, Jamila Chakir
BACKGROUND: Bronchial fibroblasts play a key role in airway remodeling in asthma. They regulate epithelial cell functions such as proliferation through growth factors, cytokines, chemokines and exosomes. The role of exosomes in the communication between epithelial cells and fibroblasts by vehiculing these mediators in asthma remains to be determined. OBJECTIVE: To evaluate the role of exosomes released by bronchial fibroblasts on epithelial cell proliferation in severe asthma...
June 26, 2017: Allergy
https://www.readbyqxmd.com/read/28649437/integrating-personalized-gene-expression-profiles-into-predictive-disease-associated-gene-pools
#2
Jörg Menche, Emre Guney, Amitabh Sharma, Patrick J Branigan, Matthew J Loza, Frédéric Baribaud, Radu Dobrin, Albert-László Barabási
Gene expression data are routinely used to identify genes that on average exhibit different expression levels between a case and a control group. Yet, very few of such differentially expressed genes are detectably perturbed in individual patients. Here, we develop a framework to construct personalized perturbation profiles for individual subjects, identifying the set of genes that are significantly perturbed in each individual. This allows us to characterize the heterogeneity of the molecular manifestations of complex diseases by quantifying the expression-level similarities and differences among patients with the same phenotype...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28638418/the-expression-of-stat3-and-stat5a-genes-in-severe-refractory-asthma
#3
Kayvan Saeedfar, Mehrdad Behmanesh, Esmaeil Mortaz, Mohammad Reza Masjedi
BACKGROUND: Despite being a high burden disorder, the pathogenesis of severe refractory asthma (SRA) is poorly understood. There are some evidences for the involvement of members of the signal transducer and activator of transcription (STAT) family, including STAT3 and STAT5a. Our study aimed to evaluate the gene expression of STAT3 and STAT5a in asthma and SRA to establish if there is an association. MATERIALS AND METHODS: Using quantitative real-time polymerase chain reactions (qRT-PCR), the transcript levels of STAT3 and STAT5a were evaluated in peripheral blood mononuclear lymphocytes (PBML) isolated from 13 patients with SRA, 14 with mild asthma, and 30 healthy volunteers...
2017: Tanaffos
https://www.readbyqxmd.com/read/28635548/th-17-regulatory-cytokines-il-21-il-23-and-il-6-enhance-neutrophil-production-of-il-17-cytokines-during-asthma
#4
Rabih Halwani, Asma Sultana, Alejandro Vazquez-Tello, Amer Jamhawi, Abeer A Al-Masri, Saleh Al-Muhsen
BACKGROUND: In a subset of severe asthma patients, chronic airway inflammation is associated with infiltration of neutrophils, Th-17 cells and elevated expression of Th-17-derived cytokines (e.g., interleukin [IL]-17, IL-21, IL-22). Peripheral neutrophils from allergic asthmatics are known to express higher IL-17 cytokine levels than those from healthy subjects, but the regulatory mechanisms involved are not well understood. We hypothesize that Th-17 regulatory cytokines could modulate IL-17 expression in neutrophils...
March 2, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28617138/targeting-transcription-factor-lysine-acetylation-in-inflammatory-airway-diseases
#5
Thea van den Bosch, Marcel Kwiatkowski, Rainer Bischoff, Frank J Dekker
Asthma and chronic obstructive pulmonary disease are inflammatory airway diseases for which alternative therapeutic strategies are urgently needed. Interestingly, HDAC inhibitors show anti-inflammatory effects in mouse models for these diseases. Here we explore underlying mechanisms that may explain these effects. In previous studies, effects of HDAC inhibitors on histone acetylation are often correlated with their effects on gene expression. However, effects of HDAC inhibitors on transcription factors and their acetylation status may be particularly important in explaining these effects...
June 15, 2017: Epigenomics
https://www.readbyqxmd.com/read/28608951/tumstatin-regulates-the-angiogenic-and-inflammatory-potential-of-airway-smooth-muscle-extracellular-matrix
#6
Louise Margaret Harkness, Markus Weckmann, Matthias Kopp, Tim Becker, Anthony Wayne Ashton, Janette Kay Burgess
The extracellular matrix (ECM) creates the microenvironment of the tissue; an altered ECM in the asthmatic airway may be central in airway inflammation and remodelling. Tumstatin is a collagen IV-derived matrikine reduced in the asthmatic airway wall that reverses airway inflammation and remodelling in small and large animal models of asthma. This study hypothesized that the mechanisms underlying the broad asthma-resolving effects of tumstatin were due to autocrine remodelling of the ECM. Neutrophils and endothelial cells were seeded on decellularized ECM of non-asthmatic (NA) or asthmatic (A) airway smooth muscle (ASM) cells previously exposed to tumstatin in the presence or absence of a broad matrix metalloproteinase inhibitor, Marimastat...
June 13, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28601047/role-of-epigenetics-in-the-pathogenesis-of-asthma
#7
Zahra Alizadeh, Esmaeil Mortaz, Ian Adcock, Mostafa Moin
Asthma is a complex, heterogeneous and chronic airway inflammatory disease with different clinical phenotypes caused by diverse triggers and pathophysiological mechanisms. Asthma heritability has been established in many genetic studies but it is evident that only genetic elements are not responsible for the development of asthma. Increasing rate of asthma incidence during past decades has implicated the role of epigenetics in development of asthma. Environmental factors perform as initiator signals through epigenetic mechanisms...
April 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28599074/beyond-epithelial-to-mesenchymal-transition-common-suppression-of-differentiation-programs-underlies-epithelial-barrier-dysfunction-in-mild-moderate-and-severe-asthma
#8
Lucas F Loffredo, Hiam Abdala-Valencia, Kishore R Anekalla, Lyda Cuervo-Pardo, Cara J Gottardi, Sergejs Berdnikovs
BACKGROUND: Epithelial barrier dysfunction is a central feature in the pathogenesis of allergic disease. Epithelial-to-mesenchymal transition (EMT) has been proposed as one mechanism afflicting barrier in asthma. However, genes and pathways involved in aberrant epithelial-mesenchymal signaling, and their relationship to asthma severity, are poorly understood. METHODS: We used unbiased gene network analysis to evaluate functional convergence in epithelial gene expression signatures across multiple public access transcriptomics datasets of human asthma, followed by text mining to evaluate functional marker relevance of discovered genes...
June 9, 2017: Allergy
https://www.readbyqxmd.com/read/28579377/dendritic-cells-conditioned-by-activin-a-induced-regulatory-t-cells-exhibit-enhanced-tolerogenic-properties-and-protect-against-experimental-asthma
#9
Maria Semitekolou, Ioannis Morianos, Aggelos Banos, Dimitris Konstantopoulos, Marina Adamou-Tzani, Tim Sparwasser, Georgina Xanthou
BACKGROUND: Previously, we have demonstrated that regulatory T (Treg) cells, induced by the cytokine activin-A, suppress Th2-mediated allergic responses and linked airway disease. Still, the effects of activin-A-induced Treg cells (act-A-iTreg cells) on the regulation of dendritic cell (DC)-driven allergic inflammation remain elusive. OBJECTIVE: Here, we investigated whether act-A-iTreg cells can modulate DC responses and endow them with enhanced tolerogenic functions...
June 1, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28579087/the-protective-role-of-helicobacter-pylori-neutrophil-activating-protein-in-childhood-asthma
#10
A Karakullukcu, H B Tokman, S Nepesov, M Demirci, S Saribas, S Vehid, R Caliskan, Z Taner, H Cokugras, T Ziver, S Demiryas, B Kocazeybek
BACKGROUND: Helicobacter pylori quantity and HP-NAP gene expression were evaluated in the faeces of healthy and asthmatic children. METHODS: H. pylori DNAs and RNAs were isolated from the stool samples of 92 asthmatic children (AC; 3-8 years) and 88 healthy controls (HC). Quantitative PCR was used to determine the quantity of H. pylori and HP-NAP expression relative to the 16S rRNA (reference gene). Gene expression was analysed using the delta delta-Ct method. RESULTS: H...
May 31, 2017: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/28574721/a-multi-omics-approach-to-identify-genes-associated-with-childhood-asthma-risk-and-morbidity
#11
Erick Forno, Ting Wang, Qi Yan, John Brehm, Edna Acosta-Perez, Angel Colon-Semidey, Maria Alvarez, Nadia Boutaoui, Michelle M Cloutier, John F Alcorn, Glorisa Canino, Wei Chen, Juan C Celedón
RATIONALE: Childhood asthma is a complex disease. In this study, we aim to identify genes associated with childhood asthma through a multi-omics "vertical" approach that integrates multiple analytical steps using linear and logistic regression models. METHODS: In a case-control study of childhood asthma in Puerto Ricans (n=1127), we use adjusted linear or logistic regression models to evaluate associations between several analytical steps of omics data, including genome-wide (GW) genotype data, GW methylation, GW expression profiling, cytokine levels, asthma-intermediate phenotypes, and asthma status...
June 2, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28559992/delivery-of-adipose-derived-mesenchymal-stem-cells-attenuates-airway-responsiveness-and-inflammation-in-a-mouse-model-of-ovalbumin-induced-asthma
#12
Ranran Dai, Jia Liu, Songbai Cai, Chengxiao Zheng, Xin Zhou
Adipose-derived mesenchymal stem cells (ADMSCs) possess immunomodulation property, yet their therapeutic potential in asthma is unclear. This study aimed to explore the effects of ADMSCs on airway hyperresponsiveness and inflammation in ovalbumin (OVA)-induced asthma models. The underlying mechanism(s) was also examined. BALB/c mice were sensitized with OVA on days 0, 7, and 14, followed by 8-week OVA challenge from day 22. ADMSCs were injected via tail vein on day 21. Animals were measured for airway responsiveness, lung pathology, IgE and cytokine levels in serum, cell composition in bronchoalveolar lavage fluid (BALF), gene expression in the lung, and regulatory T cells (Tregs)...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28552993/rhinovirus-infection-results-in-stronger-and-more-persistent-genomic-dysregulation-evidence-for-altered-innate-immune-response-in-asthmatics-at-baseline-early-in-infection-and-during-convalescence
#13
Peter W Heymann, Huyen-Tran Nguyen, John W Steinke, Ronald B Turner, Judith A Woodfolk, Thomas A E Platts-Mills, Lisa Martin, Hua He, Jocelyn Biagini Myers, Mark Lindsey, Umasundari Sivaprasad, Mario Medvedovic, Naim Mahi, Holliday Carper, Deborah D Murphy, James Patrie, Gurjit K Khurana Hershey
BACKGROUND: Rhinovirus (HRV) is associated with the large majority of virus-induced asthma exacerbations in children and young adults, but the mechanisms remain poorly defined. METHODS: Asthmatics and non-asthmatic controls were inoculated with HRV-A16, and nasal epithelial samples were obtained 7 days before, 36 hours after, and 7 days after viral inoculation. RNA was extracted and subjected to RNA-seq analysis. RESULTS: At baseline, 57 genes were differentially expressed between asthmatics and controls, and the asthmatics had decreased expression of viral replication inhibitors and increased expression of genes involved in inflammation...
2017: PloS One
https://www.readbyqxmd.com/read/28552588/vitamin-d-supplementation-during-pregnancy-effect-on-the-neonatal-immune-system-in-a-randomized-controlled-trial
#14
Eve Hornsby, Paul E Pfeffer, Nancy Laranjo, William Cruikshank, Marina Tuzova, Augusto A Litonjua, Scott T Weiss, Vincent J Carey, George O'Connor, Catherine Hawrylowicz
BACKGROUND: Programming of the immune system during fetal development can influence asthma-related risk factors and outcomes in later life. Vitamin D is a well-recognized immune modulator, and deficiency of this nutrient during pregnancy is hypothesized to influence disease development in offspring. OBJECTIVE: We sought to investigate the effect on neonatal immunity of maternal supplementation with 4400 IU/d vitamin D3 during the second and third trimesters of pregnancy by using a subset of cord blood samples from a randomized, double-blind, placebo-controlled clinical trial (the Vitamin D Antenatal Asthma Reduction Trial)...
May 16, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28529457/deguelin-attenuates-allergic-airway-inflammation-via-inhibition-of-nf-%C3%AE%C2%BAb-pathway-in-mice
#15
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-upregulation-of-il-1-receptor-family-members-in-patients-with-severe-asthma
#16
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 asthmatic patients is used to define airway inflammatory processes and might guide therapy. OBJECTIVE: We sought to determine differential gene and protein expression in sputum samples from patients with severe asthma (SA) compared with nonsmoking patients with mild/moderate asthma. METHODS: Induced sputum was obtained from nonsmoking patients with SA, smokers/ex-smokers with severe asthma, nonsmoking patients with mild/moderate asthma (MMAs), and healthy nonsmoking control subjects...
May 18, 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
#17
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
#18
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
#19
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
#20
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
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