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Asthma AND "gene expression"

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https://www.readbyqxmd.com/read/28933920/multi-tissue-transcriptomics-delineates-the-diversity-of-airway-t-cell-functions-in-asthma
#1
Akul Singhania, Joshua C Wallington, Caroline G Smith, Daniel Horowitz, Karl J Staples, Peter H Howarth, Stephan D Gadola, Ratko Djukanović, Christopher H Woelk, Timothy Sc Hinks
Asthma arises from the complex interplay of inflammatory pathways in diverse cell types and tissues. We sought to undertake a comprehensive transcriptomic assessment of the epithelium and airway T cells that remain understudied in asthma, and investigate interactions between multiple cells and tissues. Epithelial brushings and flow-sorted CD3+ T cells from sputum and bronchoalveolar lavage were obtained from healthy subjects (N=19) and asthmatic patients (mild, moderate and severe asthma; N=46). Gene expression was assessed using Affymetrix HT HG-U133+ PM GeneChips and results were validated by real-time quantitative PCR...
September 21, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28931396/il-4-induced-caveolin-1-containing-lipid-rafts-aggregation-contributes-to-muc5ac-synthesis-in-bronchial-epithelial-cells
#2
Yu Xia, Peng-Cheng Cai, Fan Yu, Liang Xiong, Xin-Liang He, Shan-Shan Rao, Feng Chen, Xiang-Ping Yang, Wan-Li Ma, Hong Ye
BACKGROUND: Mucus overproduction is an important feature of asthma. Interleukin (IL)-4 is required for allergen-induced airway inflammation and mucus production. MUC5AC gene expression is regulated by transcript factors NF-κB. The intracellular Ca(2+) ([Ca(2+)]i) signal is required for activation of NF-κB. The transient receptor potential canonical 1 (TRPC1) channel has been shown to contribute for agonist-stimulated Ca(2+) influx in some types of cells. However, the relationships among IL-4, TRPC1 and mucus overproduction in bronchial epithelial cells (BECs) in asthma are poorly understood...
September 20, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28891433/innate-lymphoid-cells-mediate-pulmonary-eosinophilic-inflammation-airway-mucous-cell-metaplasia-and-type-2-immunity-in-mice-exposed-to-ozone
#3
Kazuyoshi Kumagai, Ryan P Lewandowski, Daven N Jackson-Humbles, Nicholas Buglak, Ning Li, Kaylin White, Steven J Van Dyken, James G Wagner, Jack R Harkema
Exposure to elevated levels of ambient ozone in photochemical smog is associated with eosinophilic airway inflammation and nonatopic asthma in children. In the present study, we determined the role of innate lymphoid cells (ILCs) in the pathogenesis of ozone-induced nonatopic asthma by using lymphoid cell-sufficient C57BL/6 mice, ILC-sufficient Rag2(-/-) mice (devoid of T and B cells), and ILC-deficient Rag2(-/-)Il2rg(-/-) mice (depleted of all lymphoid cells including ILCs). Mice were exposed to 0 or 0.8 parts per million ozone for 1 day or 9 consecutive weekdays (4 hr/day)...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28888782/tnfaip3-levels-in-lung-dendritic-cells-instruct-th2-or-th17-cell-differentiation-in-eosinophilic-or-neutrophilic-asthma
#4
Heleen Vroman, Ingird M Bergen, Jennifer A C van Hulst, Memno van Nimwegen, Denise van Uden, Martin J Schuijs, Saravanan Y Pillai, Geert van Loo, Hamida Hammad, Bart N Lambrecht, Rudi W Hendriks, Mirjam Kool
BACKGROUND: It is currently unknown, why allergen exposure or environmental triggers in mild to moderate asthma patients results in Th2-mediated eosinophilic inflammation, whereas severe asthma patients often present with Th17-mediated neutrophilic inflammation. The activation state of dendritic cells (DCs) is crucial for both Th2 and Th17-cell differentiation, and is mediated through NF-κB activation. Ablation of TNFAIP3, one of the crucial negative regulators of NF-κB activation in myeloid cells and DCs was shown to control DC activation...
September 6, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28886691/impaired-response-of-the-bronchial-epithelium-to-inflammation-characterizes-severe-equine-asthma
#5
Laurence Tessier, Olivier Côté, Mary Ellen Clark, Laurent Viel, Andrés Diaz-Méndez, Simon Anders, Dorothee Bienzle
BACKGROUND: Severe equine asthma is a naturally occurring lung inflammatory disease of mature animals characterized by neutrophilic inflammation, bronchoconstriction, mucus hypersecretion and airway remodeling. Exacerbations are triggered by inhalation of dust and microbial components. Affected animals eventually are unable of aerobic performance. In this study transcriptomic differences between asthmatic and non-asthmatic animals in the response of the bronchial epithelium to an inhaled challenge were determined...
September 8, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28867182/deficiency-of-klf4-compromises-the-lung-function-in-an-acute-mouse-model-of-allergic-asthma
#6
Jeanette A Nimpong, Wintana Gebregziabher, Udai P Singh, Prakash Nagarkatti, Mitzi Nagarkatti, Johnie Hodge, Chunming Liu, Daping Fan, Walden Ai
Asthma is a chronic inflammatory disease of the airways and the mechanisms are not fully understood. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of monocytes, granulocyte and myeloid cells at early stage of differentiation. They possess phenotypic plasticity and regulate airway inflammation. We recently reported that Kruppel-like factor 4 (KLF4) regulates MDSC differentiation into fibrocytes, emerging effectors in chronic inflammation. However, the role of KLF4 in asthma is not known...
August 31, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28863172/regulation-of-xanthine-dehydrogensase-gene-expression-and-uric-acid-production-in-human-airway-epithelial-cells
#7
Ryan D Huff, Alan C-Y Hsu, Kristy S Nichol, Bernadette Jones, Darryl A Knight, Peter A B Wark, Philip M Hansbro, Jeremy A Hirota
INTRODUCTION: The airway epithelium is a physical and immunological barrier that protects the pulmonary system from inhaled environmental insults. Uric acid has been detected in the respiratory tract and can function as an antioxidant or damage associated molecular pattern. We have demonstrated that human airway epithelial cells are a source of uric acid. Our hypothesis is that uric acid production by airway epithelial cells is induced by environmental stimuli associated with chronic respiratory diseases...
2017: PloS One
https://www.readbyqxmd.com/read/28860944/chronic-asthma-and-mesenchymal-stem-cells-hyaluronan-and-airway-remodeling
#8
Benjamin D Goldstein, Mark E Lauer, Arnold I Caplan, Tracey L Bonfield
BACKGROUND: Previous studies have demonstrated that ovalbumin sensitization promotes chronic asthma phenotype in murine asthma model. Human mesenchymal stem cells (hMSCs) are multipotent cells in vitro that have been shown to decrease inflammation and can reverse airway remodeling when infused into an in vivo chronic asthma model. However, the mechanism by which hMSCs reverse remodeling is still unclear. In this study, we hypothesized that hMSCs influence remodeling by decreasing extracellular matrix (ECM) deposition, more specifically by decreasing collagen I, collagen III, and hyaluronan synthesis...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/28860381/%C3%AE-2-adrenoreceptor-is-a-regulator-of-the-%C3%AE-synuclein-gene-driving-risk-of-parkinson-s-disease
#9
Shuchi Mittal, Kjetil Bjørnevik, Doo Soon Im, Adrian Flierl, Xianjun Dong, Joseph J Locascio, Kristine M Abo, Elizabeth Long, Ming Jin, Bing Xu, Yang K Xiang, Jean-Christophe Rochet, Anders Engeland, Patrizia Rizzu, Peter Heutink, Tim Bartels, Dennis J Selkoe, Barbara J Caldarone, Marcie A Glicksman, Vikram Khurana, Birgitt Schüle, David S Park, Trond Riise, Clemens R Scherzer
Copy number mutations implicate excess production of α-synuclein as a possibly causative factor in Parkinson's disease (PD). Using an unbiased screen targeting endogenous gene expression, we discovered that the β2-adrenoreceptor (β2AR) is a regulator of the α-synuclein gene (SNCA). β2AR ligands modulate SNCA transcription through histone 3 lysine 27 acetylation of its promoter and enhancers. Over 11 years of follow-up in 4 million Norwegians, the β2AR agonist salbutamol, a brain-penetrant asthma medication, was associated with reduced risk of developing PD (rate ratio, 0...
September 1, 2017: Science
https://www.readbyqxmd.com/read/28854703/expression-quantitative-trait-loci-eqtls-in-human-placentas-suggest-developmental-origins-of-complex-diseases
#10
Shouneng Peng, Maya A Deyssenroth, Antonio F Di Narzo, Luca Lambertini, Carmen J Marsit, Jia Chen, Ke Hao
Epidemiologic studies support that at least part of the risk of chronic diseases in childhood and even adulthood may have an in utero origin, and the placenta is a key organ that plays a pivotal role in fetal growth and development. The transcriptomes of 159 human placenta tissues were profiled by genome-wide RNA sequencing (Illumina High-Seq 2500), and linked to fetal genotypes assessed by a high density single nucleotide polymorphism (SNP) genotyping array (Illumina MegaEx). Expression quantitative trait loci (eQTLs) across all annotated transcripts were mapped and examined for enrichment for disease susceptibility loci annotated in the genome-wide association studies (GWAS) catalog...
September 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28833774/corticosteroid-and-long-acting-%C3%A3-agonist-therapy-reduces-epithelial-goblet-cell-metaplasia
#11
M E Lachowicz-Scroggins, W E Finkbeiner, E D Gordon, S Yuan, L Zlock, N R Bhakta, P G Woodruff, J V Fahy, H A Boushey
BACKGROUND: Bronchial epithelial goblet cell metaplasia (GCM) with hyperplasia is a prominent feature of asthma, but the effects of treatment with corticosteroids, alone or in combination with a long-acting β2 -adrenergic receptor agonist (LABA) on GCM in the bronchial epithelium are unknown. OBJECTIVES: To determine if corticosteroid alone or in combination with a LABA alter protein and gene expression pathways associated with IL-13-induced goblet cell metaplasia...
August 22, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28796240/glucocorticoid-receptor-expression-on-circulating-leukocytes-in-healthy-and-asthmatic-adolescents-in-response-to-exercise
#12
Kim D Lu, Dan Cooper, Fadia Haddad, Frank Zaldivar, Monica Kraft, Shlomit Radom-Aizik
BackgroundPoor aerobic fitness is associated with worsening of asthma symptoms, and fitness training may improve asthma control. The mechanism linking fitness with asthma is not known. We hypothesized that repeated bouts of exercise would lead to a downregulation of glucocorticoid receptor (GR) expression on circulating leukocytes, reflecting a reduced responsiveness to stress.MethodsIn a prospective exercise training intervention of healthy and asthmatic adolescents, GR expression in leukocytes was measured using flow cytometry in response to an acute exercise challenge before and after the exercise training intervention...
August 2017: Pediatric Research
https://www.readbyqxmd.com/read/28760880/estrogen-signaling-contributes-to-sex-differences-in-macrophage-polarization-during-asthma
#13
Aleksander Keselman, Xi Fang, Preston B White, Nicola M Heller
Allergic asthma is a chronic Th2 inflammation in the lungs that constricts the airways and presents as coughing and wheezing. Asthma mostly affects boys in childhood and women in adulthood, suggesting that shifts in sex hormones alter the course of the disease. Alveolar macrophages have emerged as major mediators of allergic lung inflammation in animal models as well as humans. Whether sex differences exist in macrophage polarization and the molecular mechanism(s) that drive differential responses are not well understood...
September 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28759187/a-chinese-herbal-medicine-modified-guomin-decoction-influences-the-differentiation-of-cd4-t-cell-subsets-in-ova-induced-asthmatic-mice
#14
Lilan Qin, Yuying Lan, Jian Sun, Beiqi Zhang, Peitao Xie, Jinghui Zheng, Shuran Ma
OBJECTIVE: Modified Guomin Decoction (MGD) is an effective Chinese herbal medicine for treatment of various allergic diseases, especially allergic asthma. Its water decoction is conventionally used for treatment of allergic bronchitis in China. Up to date, the underlying mechanisms of this herbal combination have not been fully investigated yet. METHODS: In the in vivo study, the mice were treated with Chicken egg ovalbumin (OVA) and aluminum hydroxide gel as the classic allergic asthma animal model...
July 2, 2017: Neuro Endocrinology Letters
https://www.readbyqxmd.com/read/28756296/pathway-discovery-using-transcriptomic-profiles-in-adult-onset-severe-asthma
#15
Pieter-Paul Hekking, Matt J Loza, Stelios Pavlidis, Bertrand de Meulder, Diane Lefaudeux, Fred Baribaud, Charles Auffray, Ariane H Wagener, Paul Brinkman, Rene Lutter, Aruna T Bansal, Ana R Sousa, Steve A Bates, Yannis Pandis, Louise J Fleming, Dominique E Shaw, Stephen J Fowler, Y Guo, Andrea Meiser, Kai Sun, Julie Corfield, Peter H Howarth, Elisabeth H Bel, Ian M Adcock, Kian Fan Chung, Ratko Djukanovic, Peter J Sterk
BACKGROUND: Adult-onset severe asthma is characterized by highly symptomatic disease despite high-intensity asthma treatments. Understanding of the underlying pathways of this heterogeneous disease is needed for the development of targeted treatments. Gene set variation analysis is a statistical technique used to identify gene profiles in heterogeneous samples. OBJECTIVE: We sought to identify gene profiles associated with adult-onset severe asthma. METHODS: This was a cross-sectional, observational study in which adult patients with adult-onset of asthma (defined as starting at age ≥18 years) as compared with childhood-onset severe asthma (<18 years) were selected from the U-BIOPRED cohort...
July 26, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28736268/differential-connectivity-of-gene-regulatory-networks-distinguishes-corticosteroid-response-in-asthma
#16
Weiliang Qiu, Feng Guo, Kimberly Glass, Guo Cheng Yuan, John Quackenbush, Xiaobo Zhou, Kelan G Tantisira
BACKGROUND: Variations in drug response between individuals have prevented us from achieving high drug efficacy in treating many complex diseases, including asthma. Genetics plays an important role in accounting for such inter-individual variations in drug response. However, systematic approaches for addressing how genetic factors and their regulators determine variations in drug response in asthma treatment are lacking. METHODS: We used PANDA (Passing Attributes between Networks for Data Assimilations) to construct the gene regulatory networks associated with good responders and poor responders to inhaled corticosteroids based on a subset of 145 Caucasian asthmatic children who participated in the Childhood Asthma Management Cohort (CAMP)...
July 20, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28733231/tussilagonone-induced-nrf2-pathway-activation-protects-hepg2-cells-from-oxidative-injury
#17
Kyung-Mi Lee, Tae Yeon Kwon, Unwoo Kang, Eun Kyoung Seo, Ji Ho Yun, Chu Won Nho, Yeong Shik Kim
Tussilagonone is a compound derived from the medicinal plant Tussilago farfara L., which is used as a traditional medicine for respiratory diseases, including asthma and pneumonia. Recent reports suggest that tussilagonone exhibits anti-inflammatory effects; however, the scope of protective functions has not been elucidated yet. In this study, we demonstrate that tussilagonone enhances cellular detoxification by increasing quinone reductase activity in Hepa1c1c7 cells. In addition, tussilagonone decreased tert-butyl hydroperoxide(t-BHP)-induced ROS production and cell death, suggesting that it also acts as a potent antioxidant...
July 18, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28729226/solanum-paniculatum-l-decreases-levels-of-inflammatory-cytokines-by-reducing-nfkb-tbet-and-gata3-gene-expression-in-vitro
#18
Raimon Rios, Hugo Bernardino Ferreira da Silva, Norma Vilany Queiroz Carneiro, Anaque de Oliveira Pires, Tamires Cana Brasil Carneiro, Ryan Dos Santos Costa, Cintia Rodrigues Marques, Marta Santos Serafim Machado, Eudes da Silva Velozo, Telma M G da Silva, Tania M S da Silva, Adilva de Souza Conceição, Neuza Maria Alcântara-Neves, Camila Alexandrina Figueiredo
ETHNOPHARMACOLOGICAL RELEVANCE: Solanum paniculatum L., popularly known as jurubeba, is a common subtropical plant from Brazil, Paraguay, Bolivia and Argentina, that is used in folk medicine for the treatment of anemia, gastrointestinal disorders and inflammatory conditions in general. In addition to that, an ethnobotanical survey in "Todos os Santos" Bay have pointed out S. paniculatum as an herb to treat asthma. Previous publications have shown that S. paniculatum possesses antibiotic, antioxidant and modulatory effects on gastric acid secretion; however, its anti-inflammatory potential remains unexplored...
July 18, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28701525/cigarette-smoke-differentially-affects-il-13-induced-gene-expression-in-human-airway-epithelial-cells
#19
Tinne C J Mertens, Anne M van der Does, Loes E Kistemaker, Dennis K Ninaber, Christian Taube, Pieter S Hiemstra
Allergic airways inflammation in asthma is characterized by an airway epithelial gene signature composed of POSTN, CLCA1, and SERPINB2 This Th2 gene signature is proposed as a tool to classify patients with asthma into Th2-high and Th2-low phenotypes. However, many asthmatics smoke and the effects of cigarette smoke exposure on the epithelial Th2 gene signature are largely unknown. Therefore, we investigated the combined effect of IL-13 and whole cigarette smoke (CS) on the Th2 gene signature and the mucin-related genes MUC5AC and SPDEF in air-liquid interface differentiated human bronchial (ALI-PBEC) and tracheal epithelial cells (ALI-PTEC)...
July 2017: Physiological Reports
https://www.readbyqxmd.com/read/28701507/the-innate-cytokines-il-25-il-33-and-tslp-cooperate-in-the-induction-of-type-2-innate-lymphoid-cell-expansion-and-mucous-metaplasia-in-rhinovirus-infected-immature-mice
#20
Mingyuan Han, Charu Rajput, Jun Y Hong, Jing Lei, Joanna L Hinde, Qian Wu, J Kelley Bentley, Marc B Hershenson
Early-life respiratory viral infection is a risk factor for asthma development. Rhinovirus (RV) infection of 6-d-old mice, but not mature mice, causes mucous metaplasia and airway hyperresponsiveness that are associated with the expansion of lung type 2 innate lymphoid cells (ILC2s) and are dependent on IL-13 and the innate cytokine IL-25. However, contributions of the other innate cytokines, IL-33 and thymic stromal lymphopoietin (TSLP), to the observed asthma-like phenotype have not been examined. We reasoned that IL-33 and TSLP expression are also induced by RV infection in immature mice and are required for maximum ILC2 expansion and mucous metaplasia...
August 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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