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Hyperreactive Airway

A J Byrne, M Weiss, S A Mathie, S A Walker, H L Eames, D Saliba, C M Lloyd, I A Udalova
Interferon regulatory factor 5 (IRF5) is a key transcription factor involved in the control of the expression of proinflammatory cytokine and responses to infection, but its role in regulating pulmonary immune responses to allergen is unknown. We used genetic ablation, adenoviral vector-driven overexpression, and adoptive transfer approaches to interrogate the role of IRF5 in pulmonary immunity and during challenge with the aeroallergen, house dust mite. Global IRF5 deficiency resulted in impaired lung function and extracellular matrix (ECM) deposition...
October 19, 2016: Mucosal Immunology
Lauriane Galle-Treger, Yuzo Suzuki, Nisheel Patel, Ishwarya Sankaranarayanan, Jennifer L Aron, Hadi Maazi, Lin Chen, Omid Akbari
Allergic asthma is a complex and chronic inflammatory disorder that is associated with airway hyperreactivity (AHR) and driven by Th2 cytokine secretion. Type 2 innate lymphoid cells (ILC2s) produce large amounts of Th2 cytokines and contribute to the development of AHR. Here, we show that ILC2s express the α7-nicotinic acetylcholine receptor (α7nAChR), which is thought to have an anti-inflammatory role in several inflammatory diseases. We show that engagement of a specific agonist with α7nAChR on ILC2s reduces ILC2 effector function and represses ILC2-dependent AHR, while decreasing expression of ILC2 key transcription factor GATA-3 and critical inflammatory modulator NF-κB, and reducing phosphorylation of upstream kinase IKKα/β...
October 18, 2016: Nature Communications
Angela Zacharasiewicz
Maternal smoking in pregnancy (MSP) is a large modifiable risk factor for pregnancy related mortality and morbidity and also the most important known modifiable risk factor for asthma. This review summarises the effects of MSP throughout infancy, childhood and adolescence with regards to asthma (development and severity). Firstly, the direct damage caused by nicotine on fetal lung development, fetal growth and neuronal differentiation is discussed, as well as the indirect effects of nicotine on placental functioning...
July 2016: ERJ Open Research
Diamanda Rigas, Gavin Lewis, Jennifer L Aron, Bowen Wang, Homayon Banie, Ishwarya Sankaranarayanan, Lauriane Galle-Treger, Hadi Maazi, Richard Lo, Gordon J Freeman, Arlene H Sharpe, Pejman Soroosh, Omid Akbari
BACKGROUND: Atopic diseases including asthma exacerbate type 2 immune responses and involve a number of immune cell types, including regulatory T cells (Tregs) and the emerging group 2 innate lymphoid cells (ILC2s). While ILC2s are potent producers of type 2 cytokines, the regulation of ILC2 activation and function is not well understood. OBJECTIVE: In the present study, we evaluate for the first time how Tregs interact with pulmonary ILC2s and control their function...
October 4, 2016: Journal of Allergy and Clinical Immunology
Fei Xu, Xiuhua Kang, Liang Chen, Chuanhui Chen, Gen Hu, Wei Bai, Wei Zhang
Asthma is a common chronic inflammatory disease in the airways with wide prevalence, and it is thought to be caused by the combinational factors in environment and genetics. A large body of studies has suggested that cell immunity played a vital role in regulating the airway hyperreactivity (AHR) and inflammation. Therefore, we here developed a mouse model of asthma by microinjecting the pronucleus with a vector spontaneously coding human IL10 and TGFB1 gene to explore the possible interaction between these two potent molecules during asthma progression...
October 1, 2016: Transgenic Research
Xiaoqiong Su, Jue Pan, Fengxi Bai, Honglei Yuan, Nian Dong, Dandan Li, Xiangdong Wang, Zhihong Chen
BACKGROUND: Asthma is prone to Th2-mediated chronic airway inflammation. Interleukin-27 (IL-27) is a member of the IL-12 family that promotes the differentiation of Th1 cells and inhibits Th2 cells. We use human/mouse CD4(+) T cells to see whether IL-27 could inhibit IL-4 production in vitro and then observe whether IL-27 administration could alleviate allergic airway inflammation in vivo by mice asthma model. METHODS: We isolated and cultured CD4(+) T cells from healthy humans and mice to test whether IL-27 could inhibit IL-4 production under different conditions...
September 29, 2016: Journal of Translational Medicine
Jia Li, Ruping Wang, Olivia J Gannon, Alyssa C Rezey, Sixin Jiang, Brennan D Gerlach, Guoning Liao, Dale D Tang
Polo-like kinase 1 (Plk1) is a serine/threonine protein kinase that has been implicated in mitosis, cytokinesis and smooth muscle cell proliferation. The role of Plk1 in smooth muscle contraction has not been investigated. Here, stimulation with acetylcholine induced Plk1 phosphorylation at Thr-210 (an indication of Plk1 activation) in smooth muscle. Contractile stimulation also activated Plk1 in live smooth muscle cells as evidenced by changes in fluorescence resonance energy transfer signal of a Plk1 sensor...
September 23, 2016: Journal of Biological Chemistry
Nathan P Falk, Scott W Hughes, Blake C Rodgers
Chronic asthma is a major health concern for children and adults worldwide. The goal of treatment is to prevent symptoms by reducing airway inflammation and hyperreactivity. Step-up therapy for symptom control involves initiation with low-dose treatment and increasing intensity at subsequent visits if control is not achieved. Step-down therapy starts with a high-dose regimen, reducing intensity as control is achieved. Multiple randomized controlled trials have shown that inhaled corticosteroids are the most effective monotherapy...
September 15, 2016: American Family Physician
Shao-Cheng Liu, Chun-Shu Lin, Shyi-Gen Chen, Yueng-Hsiang Chu, Fei-Peng Lee, Hsuan-Hsuan Lu, Hsing-Won Wang
Both glucocorticoids and H1-antihistamines are widely used on patients with airway diseases. However, their direct effects on airway epithelial cells are not fully explored. Therefore, we use the primary culture of human nasal epithelial cells (HNEpC) to delineate in vitro mucosal responses to above two drugs. HNEpC cells were cultured with/without budesonide and azelastine. The growth rate at each group was recorded and measured as population double time (PDT). The histamine1-receptor (H1R), muscarinic1-receptor (M1R) and M3R were measured using immunocytochemistry and western blotting after 7-days treatment...
September 13, 2016: European Archives of Oto-rhino-laryngology
Linh Pham Van, Nathalie Germaud, Abdulraouf Ramadan, Nathalie Thieblemont
The contribution of dysregulated innate immune responses to the pathogenesis of allergic disease remains largely unknown. Herein, we addressed the role of Toll-like receptor signaling in airway inflammation by studying mice rendered deficient for the myeloid differentiation factor 88 (MyD88(-/-)) which results in concurrent deficiencies in TLR and IL-1R1 signaling pathways. We show that the lack of MyD88 offers a partial protection from allergic disease evidenced by reduced airway eosinophilia and production of the Th17-associated effector cytokine IL-17A...
August 26, 2016: Cellular Immunology
Whittney A Warren, Scott S Dalane, Bryce D Warren, Paul G Peterson, Rodney D Boyum, William Kelly
A 64-year-old male former smoker with a history of prostate cancer presented to our pulmonary clinic, complaining of nonproductive cough for 10 years. Prior evaluation included treatment for upper airway cough syndrome and gastroesophageal reflux, stopping angiotensin-converting enzyme inhibitor, and initiation of inhaled β-agonists. Esophageal pH monitoring indicated silent reflux, and proton pump inhibitor therapy was started. He continued to cough and complain of dyspnea. Physical examination produced unremarkable results, with no evidence of lymphadenopathy...
September 2016: Chest
Kenneth I Berger, Samantha Kalish, Yongzhao Shao, Michael Marmor, Angeliki Kazeros, Beno W Oppenheimer, Yinny Chan, Joan Reibman, Roberta M Goldring
INTRODUCTION: Small airway dysfunction occurs following WTC dust exposure, but its role in producing symptoms is unclear. METHODS: Methacholine challenge (MCT) was used to assess the relationship between onset of respiratory symptoms and small airway abnormalities in 166 symptomatic WTC dust-exposed patients. Forced oscillation testing (FOT) and respiratory symptoms were assessed during MCT. FOT parameters included resistance at 5 and 20 Hz (R5 and R20 ) and the R5 minus R20 (R5-20 )...
September 2016: American Journal of Industrial Medicine
Elisabeth Wigenstam, Linda Elfsmark, Anders Bucht, Sofia Jonasson
Inhalation of high concentrations of sulfur dioxide (SO2) affects the lungs and can be immediately dangerous to life. We examined the development of acute and long-term effects after exposure of SO2 in Sprague-Dawley rats, in particular inflammatory responses, airway hyperresponsiveness (AHR) and lung fibrosis. Animals were subjected to a single exposure of 2200ppm SO2 during 10min and treated with a single dose of the anti-inflammatory corticosteroid dexamethasone 1h following exposure. Exposed rats showed labored breathing, decreased body-weight and an acute inflammation with neutrophil and macrophage airway infiltrates 5h post exposure...
August 10, 2016: Toxicology
Isabelle Maillet, Olivier Perche, Arnaud Pâris, Olivier Richard, Aurélie Gombault, Ameziane Herzine, Jacques Pichon, Francois Huaux, Stéphane Mortaud, Bernhard Ryffel, Valérie F J Quesniaux, Céline Montécot-Dubourg
Glufosinate-ammonium (GLA), the active component of an herbicide, is known to cause neurotoxicity. GLA shares structural analogy with glutamate. It is a powerful inhibitor of glutamine synthetase (GS) and may bind to glutamate receptors. Since these potentials targets of GLA are present in lung and immune cells, we asked whether airway exposure to GLA may cause lung inflammation in mice. A single GLA exposure (1 mg/kg) induced seizures and inflammatory cell recruitment in the broncho-alveolar space, and increased myeloperoxidase (MPO), inducible NO synthase (iNOS), interstitial inflammation and disruption of alveolar septae within 6-24 h...
November 1, 2016: Clinical Science (1979-)
Lara Utsch, Adrian Logiantara, Ronald van Ree, Leonie S van Rijt
BACKGROUND: Food allergy has been associated with an increased risk for the development of allergic asthma. Asthma is a risk factor for the development of an anaphylactic response to food allergens. An immunological interplay between sensitization to different allergens in different compartments of the body might be involved. OBJECTIVE: To evaluate the immunological interplay between intragastrical peanut (PE) sensitization and respiratory sensitization to house dust mite (HDM) allergens...
August 17, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Michelle M Stein, Cara L Hrusch, Justyna Gozdz, Catherine Igartua, Vadim Pivniouk, Sean E Murray, Julie G Ledford, Mauricius Marques dos Santos, Rebecca L Anderson, Nervana Metwali, Julia W Neilson, Raina M Maier, Jack A Gilbert, Mark Holbreich, Peter S Thorne, Fernando D Martinez, Erika von Mutius, Donata Vercelli, Carole Ober, Anne I Sperling
BACKGROUND: The Amish and Hutterites are U.S. agricultural populations whose lifestyles are remarkably similar in many respects but whose farming practices, in particular, are distinct; the former follow traditional farming practices whereas the latter use industrialized farming practices. The populations also show striking disparities in the prevalence of asthma, and little is known about the immune responses underlying these disparities. METHODS: We studied environmental exposures, genetic ancestry, and immune profiles among 60 Amish and Hutterite children, measuring levels of allergens and endotoxins and assessing the microbiome composition of indoor dust samples...
August 4, 2016: New England Journal of Medicine
Thomas M Raffay, Andrew M Dylag, Juliann M Di Fiore, Laura A Smith, Helly J Einisman, Yuejin Li, Mitchell M Lakner, Ahmad M Khalil, Peter M MacFarlane, Richard J Martin, Benjamin Gaston
Bronchopulmonary dysplasia (BPD) is characterized by lifelong obstructive lung disease and profound, refractory bronchospasm. It is observed among survivors of premature birth who have been treated with prolonged supplemental oxygen. Therapeutic options are limited. Using a neonatal mouse model of BPD, we show that hyperoxia increases activity and expression of a mediator of endogenous bronchoconstriction, S-nitrosoglutathione (GSNO) reductase. MicroRNA-342-3p, predicted in silico and shown in this study in vitro to suppress expression of GSNO reductase, was decreased in hyperoxia-exposed pups...
October 2016: Molecular Pharmacology
Bharathi Aravamudan, Michael Thompson, Gary C Sieck, Robert Vassallo, Christina M Pabelick, Y S Prakash
Long-term exposure to cigarette smoke (CS) triggers airway hyperreactivity and remodeling, effects that involve airway smooth muscle (ASM). We previously showed that CS destabilizes the networked morphology of mitochondria in human ASM by regulating the expression of mitochondrial fission and fusion proteins via multiple signaling mechanisms. Emerging data link regulation of mitochondrial morphology to cellular structure and function. We hypothesized that CS-induced changes in ASM mitochondrial morphology detrimentally affect mitochondrial function, leading to CS effects on contractility and remodeling...
July 30, 2016: Journal of Cellular Physiology
Huihui You, Rui Li, Chenxi Wei, Shaohui Chen, Lin Mao, Zhenye Zhang, Xu Yang
Di-(2-ethylhexyl) phthalate (DEHP), a commonly used plasticizer, has an adjuvant effect in combination with ovalbumin (OVA). The adjuvant effect of DEHP has already been verified in our previous studies. In this study, to further investigate whether thymic stromal lymphopoietin (TSLP) was involved in the DEHP-adjuvant effect, DEHP was administered through a daily gavage exposure route. Mice were sensitized with ovalbumin (OVA) to trigger allergic responses, and an anti-TSLP monoclonal antibody was used to neutralize the effect of TSLP...
2016: PloS One
Chang-Huan Yang, Yan-Jhih Shen, Ching Jung Lai, Yu Ru Kou
Obstructive sleep apnea (OSA), manifested by airway exposure to intermittent hypoxia (IH), is associated with excess reactive oxygen species (ROS) production in airways, airway inflammation, and hyperreactive airway diseases. The cause-effect relationship for these events remains unclear. We investigated the inflammatory role of ROS-sensitive AMP-activated protein kinase (AMPK) in IH-induced airway hypersensitivity mediated by lung vagal C fibers (LVCFs) in rats. Conscious rats were exposed to room air (RA) or IH with or without treatment with N-acetyl-L-cysteine (NAC, an antioxidant), Compound C (an AMPK inhibitor), ibuprofen (a cyclooxygenase inhibitor), or their vehicles...
2016: Frontiers in Physiology
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