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Asthma AND gene expression

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https://www.readbyqxmd.com/read/29334241/transcriptional-regulation-on-the-gene-expression-signature-in-combined-allergic-rhinitis-and-asthma-syndrome
#1
Zhengdao Mao, Yujia Shi, Qi Cao, Yi Chen, Yun Sun, Zhiguang Liu, Qian Zhang, Mao Huang
AIM: This study was intended to evaluate transcriptional regulation of gene expression signatures in combined allergic rhinitis and asthma syndrome (CARAS). MATERIALS & METHODS: The blood samples of three patients with CARAS, three patients with allergic rhinitis and three normal controls were obtained. The cuffdiff, miRDeep2 and DEGseq were used to quantify the expression of genes and miRNAs, respectively. And p-value < 0.01 and false discovery rate < 0...
January 15, 2018: Epigenomics
https://www.readbyqxmd.com/read/29333270/lessons-from-ten-years-of-genome-wide-association-studies-of-asthma
#2
REVIEW
Cristina T Vicente, Joana A Revez, Manuel A R Ferreira
Twenty-five genome-wide association studies (GWAS) of asthma were published between 2007 and 2016, the largest with a sample size of 157242 individuals. Across these studies, 39 genetic variants in low linkage disequilibrium (LD) with each other were reported to associate with disease risk at a significance threshold of P<5 × 10-8, including 31 in populations of European ancestry. Results from analyses of the UK Biobank data (n=380 503) indicate that at least 28 of the 31 associations reported in Europeans represent true-positive findings, collectively explaining 2...
December 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29331643/glucagon-like-peptide-1-signaling-inhibits-allergen-induced-lung-il-33-release-and-reduces-group-2-innate-lymphoid-cell-ilc2-cytokine-production-in-vivo
#3
Shinji Toki, Kasia Goleniewska, Sara Reiss, Jian Zhang, Melissa H Bloodworth, Matthew T Stier, Weisong Zhou, Dawn C Newcomb, Lorraine B Ware, Gregg D Stanwood, Aurelio Galli, Kelli L Boyd, Kevin D Niswender, R Stokes Peebles
BACKGROUND: IL-33 is one of the most consistently associated gene candidates for asthma identified by GWAS. Studies in mice and in human cells have confirmed the importance of IL-33 in inducing type-2 cytokine production from both group 2 innate lymphoid cells (ILC2) and Th2 cells. However, there are no pharmacologic agents known to inhibit IL-33 release from airway cells. OBJECTIVE: To determine the effect of glucagon like peptide receptor-1 GLP-1R signaling on aeroallergen-induced airway IL-33 production and release and on innate type-2 airway inflammation...
January 10, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29330013/a-functional-splicing-variant-associated-with-decreased-asthma-risk-abolishes-the-ability-of-gasdermin-b-gsmdb-to-induce-epithelial-cell-pyroptosis
#4
Ronald A Panganiban, Maoyun Sun, Amber Dahlin, Hae-Ryung Park, Mengyuan Kan, Blanca E Himes, Jennifer A Mitchel, Carlos Iribarren, Eric Jorgenson, Scott H Randell, Elliot Israel, Kelan Tantisira, Stephanie Shore, Jin-Ah Park, Scott T Weiss, Ann Chen Wu, Quan Lu
BACKGROUND: Genetic variants in the chromosomal region 17q21 are consistently associated with asthma. However, mechanistic studies have not yet linked any of the associated variants to a function that could influence asthma, and as a result, the identity of the asthma gene(s) remains elusive. OBJECTIVES: We sought to identify and characterize functional variants in the 17q21 locus. METHODS: We used the Exome Aggregation Consortium (ExAC) browser to identify coding (amino acid-changing) variants in the 17q21 locus...
January 9, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29329322/methylene-tetrahydrofolate-reductase-contributes-to-allergic-airway-disease
#5
Kenneth R Eyring, Brent S Pedersen, Kenneth N Maclean, Sally P Stabler, Ivana V Yang, David A Schwartz
RATIONALE: Environmental exposures strongly influence the development and progression of asthma. We have previously demonstrated that mice exposed to a diet enriched with methyl donors during vulnerable periods of fetal development can enhance the heritable risk of allergic airway disease through epigenetic changes. There is conflicting evidence on the role of folate (one of the primary methyl donors) in modifying allergic airway disease. OBJECTIVES: We hypothesized that blocking folate metabolism through the loss of methylene-tetrahydrofolate reductase (Mthfr) activity would reduce the allergic airway disease phenotype through epigenetic mechanisms...
2018: PloS One
https://www.readbyqxmd.com/read/29317916/exposure-to-no2-co-and-pm2-5-is-linked-to-regional-dna-methylation-differences-in-asthma
#6
Mary Prunicki, Laurel Stell, Deendayal Dinakarpandian, Mariangels de Planell-Saguer, Richard W Lucas, S Katharine Hammond, John R Balmes, Xiaoying Zhou, Tara Paglino, Chiara Sabatti, Rachel L Miller, Kari C Nadeau
Background: DNA methylation of CpG sites on genetic loci has been linked to increased risk of asthma in children exposed to elevated ambient air pollutants (AAPs). Further identification of specific CpG sites and the pollutants that are associated with methylation of these CpG sites in immune cells could impact our understanding of asthma pathophysiology. In this study, we sought to identify some CpG sites in specific genes that could be associated with asthma regulation (Foxp3 and IL10) and to identify the different AAPs for which exposure prior to the blood draw is linked to methylation levels at these sites...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29307657/a-decade-of-research-on-the-17q12-21-asthma-locus-piecing-together-the-puzzle
#7
Michelle M Stein, Emma E Thompson, Nathan Schoettler, Britney A Helling, Kevin M Magnaye, Catherine Stanhope, Catherine Igartua, Andréanne Morin, Charles Washington, Dan Nicolae, Klaus Bønnelykke, Carole Ober
Chromosome 17q12-21 remains the most highly replicated and significant asthma locus. Genotypes in the core region defined by the first GWAS correlate with expression of two genes, ORMDL3 and GSDMB, making these prime candidate asthma genes, although recent studies have implicated GSDMA distal to and PGAP3 proximal to the core region as independent loci. We review here 10 years of studies on the 17q12-21 locus and suggest that genotype-specific risks for asthma at the proximal and distal loci are not specific to early onset asthma and mediated by PGAP3, ORMDL3, and/or GSDMA expression...
January 4, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29306942/targeting-neutrophils-in-severe-asthma-via-siglec-9
#8
Zi Chen, Fang-Fang Bai, Lu Han, Jin Zhu, Tao Zheng, Zhou Zhu, Lin-Fu Zhou
Severe asthma comprises only 5% of patients with asthma, but the burden it brings to the social health system accounts for more than half of all asthmatics. Clinical evidence shows that severe asthma is often linked to the recruitment and activation of neutrophils in the airways. However, the underlying molecular and immunological mechanisms of neutrophilia in severe asthma are not clear and currently available drugs exert only limited effects on neutrophilic inflammation. Great efforts are underway to address the mystery of neutrophilic inflammation in chronic respiratory disorders...
January 6, 2018: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/29305433/pinx1-and-tert-are-required-for-tnf-%C3%AE-induced-airway-smooth-muscle-chemokine-gene-expression
#9
Karl Deacon, Alan J Knox
Airway smooth muscle (ASM) cells contribute to asthmatic lung pathology with chemokine hypersecretion and increased ASM cell mass. With little recent progress in the development of asthma therapies, a greater understanding of lung inflammation mechanisms has become a priority. Chemokine gene expression in ASM cells is dependent upon NF-κB transcription factor activity. The telomerase/shelterin complex maintains chromosomal telomere ends during cell division. Telomerase is a possible cofactor for NF-κB activity, but its role in NF-κB activity in airway tissue inflammation is not known...
January 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29301585/a-randomised-pragmatic-trial-of-corticosteroid-optimization-in-severe-asthma-using-a-composite-biomarker-algorithm-to-adjust-corticosteroid-dose-versus-standard-care-study-protocol-for-a-randomised-trial
#10
Catherine E Hanratty, John G Matthews, Joseph R Arron, David F Choy, Ian D Pavord, P Bradding, Christopher E Brightling, Rekha Chaudhuri, Douglas C Cowan, Ratko Djukanovic, Nicola Gallagher, Stephen J Fowler, Tim C Hardman, Tim Harrison, Cécile T Holweg, Peter H Howarth, James Lordan, Adel H Mansur, Andrew Menzies-Gow, Sofia Mosesova, Robert M Niven, Douglas S Robinson, Dominick E Shaw, Samantha Walker, Ashley Woodcock, Liam G Heaney
BACKGROUND: Patients with difficult-to-control asthma consume 50-60% of healthcare costs attributed to asthma and cost approximately five-times more than patients with mild stable disease. Recent evidence demonstrates that not all patients with asthma have a typical type 2 (T2)-driven eosinophilic inflammation. These asthmatics have been called 'T2-low asthma' and have a minimal response to corticosteroid therapy. Adjustment of corticosteroid treatment using sputum eosinophil counts from induced sputum has demonstrated reduced severe exacerbation rates and optimized corticosteroid dose...
January 4, 2018: Trials
https://www.readbyqxmd.com/read/29298996/the-phosphatidylinositide-3-kinase-pi3k-signaling-pathway-is-a-determinant-of-zileuton-response-in-adults-with-asthma
#11
Amber Dahlin, Weiliang Qiu, Augusto A Litonjua, John J Lima, Mayumi Tamari, Michiaki Kubo, Charles G Irvin, Stephen P Peters, Ann C Wu, Scott T Weiss, Kelan G Tantisira
Variable responsiveness to zileuton, a leukotriene antagonist used to treat asthma, may be due in part to genetic variation. While individual SNPs were previously associated with zileuton-related lung function changes, specific quantitative trait loci (QTLs) and biological pathways that may contribute have not been identified. In this study, we investigated the hypothesis that genetic variation within biological pathways is associated with zileuton response. We performed an integrative QTL mapping and pathway enrichment study to investigate data from a GWAS of zileuton response, in addition to mRNA expression profiles and leukotriene production data from lymphoblastoid cell lines (LCLs) (derived from asthmatics) that were treated with zileuton or ethanol (control)...
January 3, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29284473/involvements-of-p38-mapk-and-oxidative-stress-in-the-ozone-induced-enhancement-of-ahr-and-pulmonary-inflammation-in-an-allergic-asthma-model
#12
Aihua Bao, Hong Yang, Jie Ji, Yuqin Chen, Wuping Bao, Feng Li, Min Zhang, Xin Zhou, Qiang Li, Suqin Ben
BACKGROUND: Exposure to ambient ozone (O3) increases the susceptivity to allergens and triggers exacerbations in patients with asthma. However, the detailed mechanisms of action for O3 to trigger asthma exacerbations are still unclear. METHODS: An ovalbumin (OVA)-established asthmatic mouse model was selected to expose to filtered air (OVA-model) or 1.0 ppm O3 (OVA-O3 model) during the process of OVA challenge. Next, the possible involvements of p38 MAPK and oxidative stress in the ozone actions on the asthma exacerbations were investigated on the mice of OVA-O3 model by treating them with SB239063 (a p38 MAPK inhibitor), and/or the α-tocopherol (antioxidant)...
December 29, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29262264/pde8-is-expressed-in-human-airway-smooth-muscle-and-selectively-regulates-camp-signaling-by-%C3%AE-2ar-ac6
#13
Timothy B Johnstone, Kaitlyn H Smith, Cynthia J Koziol-White, Fengying Li, Austin G Kazarian, Maia L Corpuz, Maya Shumyatcher, Frederick J Ehlert, Blanca E Himes, Reynold A Panettieri, Rennolds S Ostrom
Two cAMP signaling compartments centering around adenylyl cyclase (AC) exist in human airway smooth muscle (HASM) cells, one containing ß2AR-AC6 and another containing E prostanoid receptors (EPR)-AC2. We hypothesized that different phosphodiesterase (PDE) isozymes selectively regulate cAMP signaling in each compartment. According to RNA-seq data, 18 of 24 PDE genes were expressed in primary HASM cells derived from age- and gender-matched donors with and without asthma. PDE8A was the third most abundant of the cAMP-degrading PDE genes, after PDE4A and PDE1A...
December 20, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29250067/group-2-innate-lymphoid-cells-exhibit-a-dynamic-phenotype-in-allergic-airway-inflammation
#14
Bobby W S Li, Ralph Stadhouders, Marjolein J W de Bruijn, Melanie Lukkes, Dior M J M Beerens, Maarten D Brem, Alex KleinJan, Ingrid Bergen, Heleen Vroman, Mirjam Kool, Wilfred F J van IJcken, Tata Nageswara Rao, Hans Jörg Fehling, Rudi W Hendriks
Group 2 innate lymphoid cells (ILC2) are implicated in allergic asthma as an early innate source of the type 2 cytokines IL-5 and IL-13. However, their induction in house dust mite (HDM)-mediated airway inflammation additionally requires T cell activation. It is currently unknown whether phenotypic differences exist between ILC2s that are activated in a T cell-dependent or T cell-independent fashion. Here, we compared ILC2s in IL-33- and HDM-driven airway inflammation. Using flow cytometry, we found that surface expression levels of various markers frequently used to identify ILC2s were dependent on their mode of activation, highly variable over time, and differed between tissue compartments, including bronchoalveolar lavage (BAL) fluid, lung, draining lymph nodes, and spleen...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29248584/dexamethasone-inhibits-inflammatory-response-via-down-regulation-of-ap-1-transcription-factor-in-human-lung-epithelial-cells
#15
Rajeshwari H Patil, M Naveen Kumar, K M Kiran Kumar, Rashmi Nagesh, K Kavya, R L Babu, Govindarajan T Ramesh, S Chidananda Sharma
The production of inflammatory mediators by epithelial cells in inflammatory lung diseases may represent an important target for the anti-inflammatory effects of glucocorticoids. Activator protein-1 (Khanapure et al.) is a major activator of inflammatory genes and has been proposed as a target for inhibition by glucocorticoids. We have used human pulmonary type-II A549 cells to examine the effect of dexamethasone on the phorbol ester (PMA)/Lipopolysaccharide (LPS) induced pro-inflammatory cytokines and AP-1 factors...
December 14, 2017: Gene
https://www.readbyqxmd.com/read/29242385/differential-regulation-of-zfp30-expression-in-murine-airway-epithelia-through-altered-binding-of-zfp148-to-rs51434084
#16
Lucas T Laudermilk, Joseph M Thomas, Samir N Kelada
Neutrophil chemotaxis to the airways is a key aspect of host response to microbes and a feature of multiple pulmonary diseases including asthma. Tight regulation of this recruitment is critical to prevent unwanted host tissue damage and inflammation. Using a mouse (Mus musculus) model of asthma applied to the Collaborative Cross (CC), we previously identified a lung gene expression quantitative trait locus (eQTL) for Zinc finger protein 30 (Zfp30) that was also a QTL for neutrophil recruitment and the hallmark neutrophil chemokine CXCL1...
December 14, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29242170/a-shift-in-the-il-6-stat3-signalling-pathway-imbalance-towards-the-shp2-pathway-in-severe-asthma-results-in-reduced-proliferation-process
#17
Ikhlass Haj Salem, Sophie Plante, Abdelilah S Gounni, Mahmoud Rouabhia, Jamila Chakir
BACKGROUND: Bronchial fibroblasts are the main structural cells responsible for extracellular matrix production and turnover in lung tissue. They play a key role in airway remodelling in asthma through different cytokines including interleukin (IL-6). OBJECTIVE: To decipher IL-6 signalling in bronchial fibroblasts obtained from severe eosinophilic asthmatics compared to mild asthmatics and healthy controls. METHODS: Human bronchial fibroblasts were isolated from bronchial biopsies of mild and severe eosinophilic asthmatics and non-atopic healthy controls...
December 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29235261/interferon-%C3%AE-2-and-interferon-%C3%AE-induce-the-degranulation-independent-production-of-vegf-a-and-il-1-receptor-antagonist-and-other-mediators-from-human-mast-cells
#18
Sharon A Oldford, Suzanne P Salsman, Liliana Portales-Cervantes, Raidan Alyazidi, Robert Anderson, Ian D Haidl, Jean S Marshall
BACKGROUND: Mast cells are resident immune effector cells, often studied in the context of allergic disease. Found in substantial numbers at sites of potential infection they are increased at sites of angiogenesis and can be pivotal for the sensing and clearance of a variety of pathogens. Interferons (IFNs) are cytokines that are critical for host defence against intracellular pathogens. Increased levels of IFNs are observed during viral infection and in autoimmune diseases. IFNs are also widely used therapeutically and have been examined in the therapy of severe asthma...
December 13, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/29231896/differential-expression-of-serum-micrornas-supports-cd4%C3%A2-%C2%BA-t-cell-differentiation-into-th2-th17-cells-in-severe-equine-asthma
#19
Alicja Pacholewska, Matthias F Kraft, Vincent Gerber, Vidhya Jagannathan
MicroRNAs (miRNAs) regulate post-transcriptional gene expression and may be exported from cells via exosomes or in partnership with RNA-binding proteins. MiRNAs in body fluids can act in a hormone-like manner and play important roles in disease initiation and progression. Hence, miRNAs are promising candidates as biomarkers. To identify serum miRNA biomarkers in the equine model of asthma we investigated small RNA derived from the serum of 34 control and 37 asthmatic horses. These samples were used for next generation sequencing, novel miRNA identification and differential miRNA expression analysis...
December 12, 2017: Genes
https://www.readbyqxmd.com/read/29228930/gene-expression-analysis-in-asthma-using-a-targeted-multiplex-array
#20
Christopher D Pascoe, Ma'en Obeidat, Bryna A Arsenault, Yunlong Nie, Stephanie Warner, Dorota Stefanowicz, Samuel J Wadsworth, Jeremy A Hirota, S Jasemine Yang, Delbert R Dorscheid, Chris Carlsten, Tillie L Hackett, Chun Y Seow, Peter D Paré
BACKGROUND: Gene expression changes in the structural cells of the airways are thought to play a role in the development of asthma and airway hyperresponsiveness. This includes changes to smooth muscle contractile machinery and epithelial barrier integrity genes. We used a targeted gene expression arrays to identify changes in the expression and co-expression of genes important in asthma pathology. METHODS: RNA was isolated from the airways of donor lungs from 12 patients with asthma (8 fatal) and 12 non-asthmatics controls and analyzed using a multiplexed, hypothesis-directed platform to detect differences in gene expression...
December 11, 2017: BMC Pulmonary Medicine
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