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Asthma AND "gene expression"

Mei Mei, Haojun Song, Lina Chen, Bin Hu, Ru Bai, Diandou Xu, Ying Liu, Yuliang Zhao, Chunying Chen
BACKGROUND: Epidemiological studies have suggested that elevated levels of air pollution contribute to an increased incidence or severity of asthma. Although late-onset adult asthma seems to be more attributable to environmental risk factors, limited data is available on the impact of early-life exposure to size-fractionated ambient particulate matter (PM) on asthma in adults. We aimed to determine the effect on the development and exacerbation of asthma in the adult after the mice were exposed as juveniles to three size-fractionated ambient particulates collected from Beijing...
March 14, 2018: Particle and Fibre Toxicology
Allison K Farrell, Richard B Slatcher, Erin T Tobin, Ledina Imami, Derek E Wildman, Francesca Luca, Samuele Zilioli
The glucocorticoid receptor gene NR3C1 is an important down-regulator of inflammation and is typically under-expressed in individuals with low socioeconomic status (SES). Negative emotionality has been suggested as a potential mediator of SES disparities in health outcomes. In this study, we expand this literature by naturalistically assessing negative emotionality in a key emotional environment: the family. In a sample of 104 youth with asthma (10-17 years) and their primary caregiver, we assessed SES via caregiver report, emotional expression by youth and parents in the home over four days using the electronically activated recorder (EAR), and NR3C1 expression via blood collected from youth...
February 15, 2018: Psychoneuroendocrinology
Michael C Peters, Sheena Kerr, Eleanor M Dunican, Prescott G Woodruff, Merritt L Fajt, Bruce D Levy, Elliot Israel, Brenda R Phillips, David T Mauger, Suzy A Comhair, Serpil C Erzurum, Mats W Johansson, Nizar N Jarjour, Andrea M Coverstone, Mario Castro, Annette T Hastie, Eugene R Bleecker, Sally E Wenzel, John V Fahy
BACKGROUND: Airway type 2 inflammation is usually corticosteroid sensitive, but the role of type 2 inflammation as a mechanism of asthma in patients on high dose inhaled corticosteroids (ICS) is uncertain. OBJECTIVE: To determine if airway type 2 inflammation persists in patients treated with ICS and to evaluate the clinical features of patients with steroid resistant airway type-2 inflammation. METHODS: We used qPCR to generate a composite metric of type-2 cytokine gene expression (type 2 Gene Mean, "T2GM") in induced sputum cells from healthy controls, severe asthma patients on ICS (n=174), and non-severe asthma patients on ICS (n=85)...
March 7, 2018: Journal of Allergy and Clinical Immunology
Charu Rajput, Megan P Walsh, Breanna N Eder, Ediri E Metitiri, Antonia P Popova, Marc B Hershenson
Infections with rhinovirus (RV) cause asthma exacerbations. Recent studies suggest that macrophages play a role in asthmatic airway inflammation and the innate immune response to RV infection. Macrophages exhibit discrete phenotypes based on surface markers and gene expression. We hypothesized that macrophage polarization state alters gene expression in response to RV infection. Cells were derived from human peripheral blood derived monocytes. M1 and M2 polarization was carried out using IFN-y and IL-4, respectively, and RNA was extracted for Affymetrix Human Gene ST2...
March 9, 2018: Physiological Genomics
Yu-Li Liu, Li-de Zhang, Tie-Ming Ma, Si-Tong Song, Hai-Tao Liu, Xu Wang, Ning Li, Chang Yang, Song Yu
Acupuncture was proven beneficial in treating allergic inflammation. We aimed to explore the regulation underlying the effects of acupuncture on Feishu, an acupoint most commonly used in the acupuncture therapy for respiratory diseases, with respect to the system of sympathetic nerve neurotransmitter acetylcholine (Ach). Male Wistar rats were randomly grouping. No treatment was taken in the normal group. Allergic asthma was induced using ovalbumin on the model, Feishu acupuncture, and sham acupuncture groups; then control or acupuncture treatment lasting for 3 weeks was performed...
March 8, 2018: Inflammation
Matthew C Altman, Elizabeth Whalen, Alkis Togias, George T O'Connor, Leonard B Bacharier, Gordon R Bloomberg, Meyer Kattan, Robert A Wood, Scott Presnell, Petra LeBeau, Katy Jaffee, Cynthia M Visness, William W Busse, James E Gern
BACKGROUND: Childhood asthma in inner city populations is a major public health burden and understanding early life immune mechanisms that promote asthma onset is key to disease prevention. Children who develop asthma demonstrate a high prevalence of aeroallergen sensitization and T helper 2 (Th2)-type inflammation, however the early life immune events that lead to Th2 skewing and disease development are unknown. OBJECTIVE: We sought to use RNA sequencing of peripheral blood mononuclear cells (PBMCs) collected at age 2 to determine networks of immune responses that occur in children who develop allergy and asthma...
March 5, 2018: Journal of Allergy and Clinical Immunology
Junfei Wang, Alen Faiz, Qi Ge, Cornelis J Vermeulen, Joanne Van der Velden, Kenneth J Snibson, Rob van de Velde, Sonia Sawant, Dikaia Xenaki, Brian Oliver, Wim Timens, Nick Ten Hacken, Maarten van den Berge, Alan James, John G Elliot, Liang Dong, Janette K Burgess, Anthony W Ashton
Neovascularization, increased basal membrane thickness and increased airway smooth muscle (ASM) bulk are hallmarks of airway remodelling in asthma. In this study, we examined connective tissue growth factor (CTGF) dysregulation in human lung tissue and animal models of allergic airway disease. Immunohistochemistry revealed that ASM cells from patients with severe asthma (A) exhibited high expression of CTGF, compared to mild and non-asthmatic (NA) tissues. This finding was replicated in a sheep model of allergic airways disease...
March 7, 2018: Journal of Cellular and Molecular Medicine
Bo Sun, Linnan Zhu, Yaling Tao, Hai-Xi Sun, Yang Li, Peng Wang, Yuzhu Hou, Yang Zhao, Xiaodong Zhang, Lianfeng Zhang, Ning Na, Yong Zhao
Neutrophils are involved in the pathogenesis of allergy. However, the contribution of the different functionally polarized neutrophils in allergy needs to be clarified. We sought to define the characteristics of interleukin (IL)-33-induced neutrophils and the involvement of this subset of polarized neutrophils in allergic pathogenesis. Freshly isolated neutrophils were treated with different cytokines and the cytokine expression levels were detected by real-time PCR. The gene expression profile of IL-33-induced neutrophils was determined by microarray assay...
March 5, 2018: Cellular & Molecular Immunology
Tetsuo Miyake, Takashi Miyake, Makoto Sakaguchi, Hirokazu Nankai, Takahiro Nakazawa, Ryuichi Morishita
Transactivation of inflammatory and immune mediators in asthma is tightly regulated by nuclear factor κB (NF-κB) and signal transducer and activator of transcription 6 (STAT6). Therefore, we investigated the efficacy of simultaneous inhibition of NF-κB and STAT6 using a chimeric decoy strategy to prevent asthma exacerbation. The effects of decoy oligodeoxynucleotides were evaluated using an ovalbumin-induced mouse asthma model. Ovalbumin-sensitized mice received intratracheal administration of decoy oligodeoxynucleotides 3 days before ovalbumin challenge...
March 2, 2018: Molecular Therapy. Nucleic Acids
Cheng-Jian Xu, Cilla Söderhäll, Mariona Bustamante, Nour Baïz, Olena Gruzieva, Ulrike Gehring, Dan Mason, Leda Chatzi, Mikel Basterrechea, Sabrina Llop, Maties Torrent, Francesco Forastiere, Maria Pia Fantini, Karin C Lødrup Carlsen, Tari Haahtela, Andréanne Morin, Marjan Kerkhof, Simon Kebede Merid, Bianca van Rijkom, Soesma A Jankipersadsing, Marc Jan Bonder, Stephane Ballereau, Cornelis J Vermeulen, Raul Aguirre-Gamboa, Johan C de Jongste, Henriette A Smit, Ashish Kumar, Göran Pershagen, Stefano Guerra, Judith Garcia-Aymerich, Dario Greco, Lovisa Reinius, Rosemary R C McEachan, Raf Azad, Vegard Hovland, Petter Mowinckel, Harri Alenius, Nanna Fyhrquist, Nathanaël Lemonnier, Johann Pellet, Charles Auffray, Pieter van der Vlies, Cleo C van Diemen, Yang Li, Cisca Wijmenga, Mihai G Netea, Miriam F Moffatt, William O C M Cookson, Josep M Anto, Jean Bousquet, Tiina Laatikainen, Catherine Laprise, Kai-Håkon Carlsen, Davide Gori, Daniela Porta, Carmen Iñiguez, Jose Ramon Bilbao, Manolis Kogevinas, John Wright, Bert Brunekreef, Juha Kere, Martijn C Nawijn, Isabella Annesi-Maesano, Jordi Sunyer, Erik Melén, Gerard H Koppelman
BACKGROUND: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. METHODS: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4-5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design...
February 26, 2018: Lancet Respiratory Medicine
Niloufar Farzan, Susanne J Vijverberg, Michael Kabesch, Peter J Sterk, Anke H Maitland-van der Zee
Asthma is a complex multifactorial disease and it is the most common chronic disease in children. There is a high variability in response to asthma treatment, even in patients with good adherence to maintenance treatment, and a correct inhalation technique. Distinct underlying disease mechanisms in childhood asthma might be the reason of this heterogeneity. A deeper knowledge of the underlying molecular mechanisms of asthma has led to the recent development of advanced and mechanism-based treatments such as biologicals...
March 1, 2018: Pediatric Pulmonology
Ralph Stadhouders, Bobby W S Li, Marjolein J W de Bruijn, Antonio Gomez, Tata Nageswara Rao, Hans Jörg Fehling, Wilfred F J van IJcken, Ai Ing Lim, James P Di Santo, Thomas Graf, Rudi W Hendriks
BACKGROUND: Group 2 innate lymphoid cells (ILC2s) are major producers of cytokines driving allergic asthma and elevated numbers of ILC2s have been detected in blood and sputum of asthma patients. Asthma susceptibility has a strong genetic component, but the underlying mechanisms and whether asthma genetics impact ILC2 biology remains unclear. OBJECTIVE: To study the ILC2 transcriptome and epigenome during airway inflammation (AI) in order to couple these to genes and genetic variants associated with asthma pathogenesis...
February 24, 2018: Journal of Allergy and Clinical Immunology
E Tóth, T Tornóczky, J Kneif, A Perkecz, K Katona, Z Piski, Á Kemény, I Gerlinger, J Szolcsányi, J Kun, E Pintér
BACKGROUND: Chronic rhinosinusitis (CRS) is a multifactorial upper airway disease with unclear etiology. Neuronal Transient Receptor Potential Vanilloid 1 (TRPV1) and Ankyrin 1 (TRPA1) channels have been implicated in the pathogenesis of CRS. We aimed to detect the expression of extraneuronal TRPV1 and TRPA1 receptors in nasal polyp (NP) tissue samples. METHODOLOGY: Samples were obtained from fourty-two CRS pateints with nasal polyp and sixteen healthy controls to measure receptor gene expression by quantitative PCR, protein localization by immunohistochemistry and cytokine profile by multiplex bead immunoassay...
February 24, 2018: Rhinology
Tara L Croston, Angela R Lemons, Donald H Beezhold, Brett J Green
Fungal bioaerosols are ubiquitous in the environment and human exposure can result in a variety of health effects ranging from systemic, subcutaneous, and cutaneous infections to respiratory morbidity including allergy, asthma, and hypersensitivity pneumonitis. Recent research has focused on the role of microRNAs (miRNAs) following fungal exposure and is overlooked, yet important, group of regulators capable of influencing fungal immune responses through a variety of cellular mechanisms. These small non-coding ribose nucleic acids function to regulate gene expression at the post-transcriptional level and have been shown to participate in multiple disease pathways including cancer, heart disease, apoptosis, as well as immune responses to microbial hazards and occupational allergens...
2018: Frontiers in Immunology
José A Cañas, Beatriz Sastre, José M Rodrigo-Muñoz, Mar Fernández-Nieto, Pilar Barranco, Santiago Quirce, Joaquín Sastre, Victoria Del Pozo
BACKGROUND: Eosinophils, a central factor in asthma pathogenesis, have the ability to secrete exosomes. However, the precise role played by exosomes in the biological processes leading up to asthma has not been fully defined. OBJECTIVE: We hypothesised that exosomes released by eosinophils contribute to asthma pathogenesis by activating structural lung cells. METHODS: Eosinophils from asthmatic patients and healthy volunteers were purified from peripheral blood, and exosomes were isolated from eosinophils of asthmatic and healthy individuals...
February 16, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Sylwia Moskwa, Wojciech Piotrowski, Jerzy Marczak, Małgorzata Pawełczyk, Anna Lewandowska-Polak, Marzanna Jarzębska, Małgorzata Brauncajs, Anna Głobińska, Paweł Górski, Nikolaos G Papadopoulos, Michael R Edwards, Sebastian L Johnston, Marek L Kowalski
PURPOSE: In order to gain an insight into determinants of reported variability in immune responses to respiratory viruses in human bronchial epithelial cells (HBECs) from asthmatics, the responses of HBEC to viral infections were evaluated in HBECs from phenotypically heterogeneous groups of asthmatics and in healthy controls. METHODS: HBECs were obtained during bronchoscopy from 10 patients with asthma (6 atopic and 4 non-atopic) and from healthy controls (n=9) and grown as undifferentiated cultures...
March 2018: Allergy, Asthma & Immunology Research
Cody McHale, Zahraa Mohammed, Juline Deppen, Gregorio Gomez
BACKGROUND: Interleukin-6 is a gp130 utilizing cytokine that is consistently associated with allergic diseases like asthma and urticaria in humans where mast cells are known to play a critical role. However, the role of IL-6 in allergic disease in not known. IL-6 was reported to enhance degranulation of in vitro-derived mast cells, but the effect of IL-6 on mediator release from human in situ-matured tissue-isolated mast cells had not been reported. METHODS: Human mature mast cells were isolated and purified from normal skin tissue from different donors...
February 1, 2018: Biochimica et Biophysica Acta
Elizabeth J Davidson, Ivana V Yang
PURPOSE OF REVIEW: Epigenetic marks are emerging as mediators of genetics and the environment on complex disease phenotypes, including childhood asthma and allergy. RECENT FINDINGS: Epigenome-wide association studies over the past year have added to the growing body of evidence supporting significant associations of epigenetic regulation of gene expression and asthma and allergy. Studies in children have identified signatures of eosinophils in peripheral blood, Th2 cell transcription factors and cytokines in peripheral blood mononuclear cells, and epithelial dysfunction in the respiratory epithelium...
January 31, 2018: Current Opinion in Allergy and Clinical Immunology
Junfei Zhao, Feixiong Cheng, Peilin Jia, Nancy Cox, Joshua C Denny, Zhongming Zhao
BACKGROUND: Genome-phenome studies have identified thousands of variants that are statistically associated with disease or traits; however, their functional roles are largely unclear. A comprehensive investigation of regulatory mechanisms and the gene regulatory networks between phenome-wide association study (PheWAS) and genome-wide association study (GWAS) is needed to identify novel regulatory variants contributing to risk for human diseases. METHODS: In this study, we developed an integrative functional genomics framework that maps 215,107 significant single nucleotide polymorphism (SNP) traits generated from the PheWAS Catalog and 28,870 genome-wide significant SNP traits collected from the GWAS Catalog into a global human genome regulatory map via incorporating various functional annotation data, including transcription factor (TF)-based motifs, promoters, enhancers, and expression quantitative trait loci (eQTLs) generated from four major functional genomics databases: FANTOM5, ENCODE, NIH Roadmap, and Genotype-Tissue Expression (GTEx)...
January 29, 2018: Genome Medicine
Kentaro Tamura, Koichiro Matsumoto, Satoru Fukuyama, Keiko Kan-O, Yumiko Ishii, Ken Tonai, Miyoko Tatsuta, Aimi Enokizu, Hiromasa Inoue, Yoichi Nakanishi
Asthma and chronic obstructive pulmonary disease (COPD), chronic airway inflammatory diseases characterized by airflow limitation, have different etiologies and pathophysiologies. Asthma-COPD Overlap (ACO) has recently been used for patients with mixed asthma and COPD. The pathophysiological mechanisms of ACO have not been clearly understood due to the lack of an appropriate murine model. To investigate its pathophysiology, we examined a murine model by allergen challenge in surfactant protein-D (SP-D)-deficient mice that spontaneously developed pulmonary emphysema...
January 2018: Physiological Reports
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