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https://www.readbyqxmd.com/read/28619712/targeting-acetylcholine-receptor-m3-prevents-the-progression-of-airway-hyperreactivity-in-a-mouse-model-of-childhood-asthma
#1
Kruti R Patel, Yan Bai, Kenneth G Trieu, Juliana Barrios, Xingbin Ai
Asthma often progresses into adulthood from early-life episodes of adverse environmental exposures. However, how the injury to developing lungs contributes to the pathophysiology of persistent asthma remains poorly understood. In this study, we identified an age-related mechanism along the cholinergic nerve-airway smooth muscle (ASM) axis that underlies prolonged airway hyperreactivity (AHR) in mice. We showed that ASM continued to mature until ∼3 wk after birth. Coinciding with postnatal ASM maturation, there was a critical time window for the development of ASM hypercontractility after cholinergic stimulation...
June 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28579374/activated-plasmacytoid-dendritic-cells-regulate-type-2-innate-lymphoid-cells-mediated-airway-hyperreactivity
#2
Hadi Maazi, Homayon Banie, German Aleman, Nisheel Patel, Bowen Wang, Ishwarya Sankaranarayanan, Vipul Bhargava, Takahiro Sato, Gavin Lewis, Matteo Cesaroni, James Karras, Anuk Das, Pejman Soroosh, Omid Akbari
BACKGROUND: Allergic asthma is a prevalent inflammatory disease of the airways caused by dysregulated immune balance in the lungs with incompletely understood pathogenesis. The recently identified type 2 innate lymphoid cells (ILC2s) play significant roles in the pathogenesis of asthma. While ILC2-activating factors have been identified, the mechanisms that suppress ILC2s remain largely unknown. Plasmacytoid dendritic cells, pDCs, are important in antiviral immunity and in maintaining tolerance to inert antigens...
June 1, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28570267/allergen-encoding-bone-marrow-transfer-inactivates-allergic-t-cell-responses-alleviating-airway-inflammation
#3
Jane Al-Kouba, Andrew N Wilkinson, Malcolm R Starkey, Rajeev Rudraraju, Rhiannon B Werder, Xiao Liu, Soi-Cheng Law, Jay C Horvat, Jeremy F Brooks, Geoffrey R Hill, Janet M Davies, Simon Phipps, Philip M Hansbro, Raymond J Steptoe
Memory Th2 cell responses underlie the development and perpetuation of allergic diseases. Because these states result from immune dysregulation, established Th2 cell responses represent a significant challenge for conventional immunotherapies. New approaches that overcome the detrimental effects of immune dysregulation are required. We tested whether memory Th2 cell responses were silenced using a therapeutic approach where allergen expression in DCs is transferred to sensitized recipients using BM cells as a vector for therapeutic gene transfer...
June 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/28568169/effect-of-dexamethasone-and-fluticasone-on-airway-hyperresponsiveness-in-horses-with-inflammatory-airway-disease
#4
R Léguillette, T Tohver, S L Bond, J A Nicol, K J McDonald
BACKGROUND: Airway hyperresponsiveness (AWHR), expressed as hypersensitivity (PC75 RL ) or hyperreactivity (slope of the histamine dose-response curve), is a feature of inflammatory airway disease (IAD) or mild equine asthma in horses. Glucocorticoids are used empirically to treat IAD. OBJECTIVES: To determine whether dexamethasone (DEX) (0.05 mg/kg IM q24h) and inhaled fluticasone (FLUT) (3,000 μg q12h) administered by inhalation are effective in decreasing AWHR, lung inflammation, and clinical signs in horses with IAD...
May 31, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28555112/caveolin-1-functional-insights-into-its-role-in-muscarine-and-serotonin-induced-smooth-muscle-constriction-in-murine-airways
#5
Maryam Keshavarz, Heike Schwarz, Petra Hartmann, Silke Wiegand, Melanie Skill, Mike Althaus, Wolfgang Kummer, Gabriela Krasteva-Christ
An increased bronchoconstrictor response is a hallmark in the progression of obstructive airway diseases. Acetylcholine and 5-hydroxytryptamine (5-HT, serotonin) are the major bronchoconstrictors. There is evidence that both cholinergic and serotonergic signaling in airway smooth muscle (ASM) involve caveolae. We hypothesized that caveolin-1 (cav-1), a structural protein of caveolae, plays an important regulatory role in ASM contraction. We analyzed airway contraction in different tracheal segments and extra- and intrapulmonary bronchi in cav-1 deficient (cav-1-/-) and wild-type mice using organ bath recordings and videomorphometry of methyl-beta-cyclodextrin (MCD) treated and non-treated precision-cut lung slices (PCLS)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28546155/long-term-nicotine-exposure-dampens-lps-induced-nerve-mediated-airway-hyperreactivity-in-murine-airways
#6
Yuan Xu, Lars-Olaf Cardell
Nicotine is a major component of cigarette smoke. It causes addiction and is used clinically to aid smoke cessation. The aim of the present study is to investigate the effect of nicotine on lipopolysaccharide (LPS)-induced airway hyperreactivity (AHR) and to explore the potential involvement of neuronal mechanisms behind nicotine's effects in murine models in vivo and in vitro. BALB/c mice were exposed to nicotine in vivo via subcutaneous Alzet osmotic minipumps containing nicotine tartate salt solution (24 mg/kg/day) for 28 days...
May 25, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28543086/allergen-immunotherapy-for-allergic-asthma-a-systematic-review-and-meta-analysis
#7
REVIEW
Sangeeta Dhami, Artemisia Kakourou, Felix Asamoah, Ioana Agache, Susanne Lau, Jutel Marek, Antonella Muraro, Graham Roberts, Cezmi A Akdis, Matteo Bonini, Ozlem Cavkaytar, Breda Flood, Pawel Gajdanowicz, Kenji Izuhara, Ömer Kalayci, Ralph Mosges, Oscar Palomares, Oliver Pfaar, Sylwia Smolinska, Milena Sokolowska, Miqdad Asaria, Gopal Netuveli, Hader Zaman, Ather Akhlaq, Aziz Sheikh
BACKGROUND: To inform the development of the European Academy of Allergy and Clinical Immunonology's (EAACI) Guidelines on Allergen Immunotherapy (AIT) for allergic asthma, we assessed the evidence on the effectiveness, cost-effectiveness and safety of AIT. METHODS: We performed a systematic review, which involved searching nine databases. Studies were screened against pre-defined eligibility criteria and critically appraised using established instruments. Data were synthesized using random-effects meta-analyses...
May 19, 2017: Allergy
https://www.readbyqxmd.com/read/28534960/cellular-na-handling-mechanisms-involved-in-airway-smooth-muscle-contraction-review
#8
Bettina Sommer, Edgar Flores-Soto, Georgina Gonzalez-Avila
A decrease in bronchial diameter is designated as bronchoconstriction (BC) and impedes the flow of air through the airway. Asthma is characterized by inflammation of the airways, reversible BC and nonspecific hyperreactivity. These last two symptoms are dependent on airway smooth muscle. Stimuli that trigger contraction can be characterized as chemical (neurotransmitters, cytokines and terpenoids) and physical (volume inspired, air pressure). Both stimuli activate signaling pathways by acting on membrane proteins and facilitating the passage of ions through the membrane, generating a voltage change and a subsequent depolarization...
May 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28532656/the-il-33-st2-axis-is-crucial-in-type-2-airway-responses-induced-by-the-staphylococcus-aureus-protease-spld
#9
Andrea R Teufelberger, Maria Nordengrün, Harald Braun, Tania Maes, Katrien De Grove, Gabriele Holtappels, Clara O'Brien, Sharen Provoost, Hamida Hammad, Amanda Gonçalves, Rudi Beyaert, Wim Declercq, Peter Vandenabeele, Dmitri V Krysko, Barbara M Bröker, Claus Bachert, Olga Krysko
BACKGROUND: Chronic airway inflammatory diseases such as chronic rhinosinusitis with nasal polyps and asthma showed increased nasal Staphylococcus aureus (S. aureus) colonization. Serine protease like protein D (SplD) and other closely related proteases secreted by S. aureus have recently been identified as inducers of allergic asthma in humans and mice but their mechanism of action is largely unknown. OBJECTIVE: We investigated the role of recombinant SplD in driving Th2-biased responses and IgE formation in a murine model of allergic asthma...
May 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28515358/irf5-distinguishes-severe-asthma-in-humans-and-drives-th1-phenotype-and-airway-hyperreactivity-in-mice
#10
Timothy B Oriss, Mahesh Raundhal, Christina Morse, Rachael E Huff, Sudipta Das, Rachel Hannum, Marc C Gauthier, Kathryn L Scholl, Krishnendu Chakraborty, Seyed M Nouraie, Sally E Wenzel, Prabir Ray, Anuradha Ray
Severe asthma (SA) is a significant problem both clinically and economically, given its poor response to corticosteroids (CS). We recently reported a complex type 1-dominated (IFN-γ-dominated) immune response in more than 50% of severe asthmatics despite high-dose CS treatment. Also, IFN-γ was found to be critical for increased airway hyperreactivity (AHR) in our model of SA. The transcription factor IRF5 expressed in M1 macrophages can induce a Th1/Th17 response in cocultured human T cells. Here we show markedly higher expression of IRF5 in bronchoalveolar lavage (BAL) cells of severe asthmatics as compared with that in cells from milder asthmatics or healthy controls...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28510479/increased-expression-of-p22phox-mediates-airway-hyperresponsiveness-in-an-experimental-model-of-asthma
#11
Chandran Nagaraj, Hans Michael Haitchi, Akos Heinemann, Peter Howarth, Andrea Olschewski, Leigh M Marsh
AIM: Chronic airway diseases such as asthma are associated with increased production of reactive oxygen species (ROS) and oxidative stress. Endogenous NADPH oxidases are a major source of superoxide in lung, but their underlying role in asthma pathology is poorly understood. We sought to characterize the involvement of NADPH oxidase in allergic asthma by studying the role of CYBA (p22phox) in human asthma and murine house dust mite (HDM)-induced allergic airway inflammation. RESULTS: Increased expression and localisation of p22-PHOX was observed in biopsies of asthmatic patients...
May 16, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28494199/fine-particulate-matter-pm2-5-enhances-allergic-sensitization-in-balb-c-mice
#12
Alejandro R Castañeda, Keith J Bein, Suzette Smiley-Jewell, Kent E Pinkerton
Ambient particulate matter (PM), a component of air pollution, exacerbates airway inflammation and hyperreactivity in asthmatic patients. Studies showed that PM possesses adjuvant-like properties that enhance the allergic inflammatory response; however, the mechanism (or mechanisms) by which PM enhances the allergic response remains to be determined. The aim of this study was to assess how exposure to fine PM collected from Sacramento, CA, shapes the allergic airway immune response in BALB/c mice undergoing sensitization and challenge with ovalbumin (OVA)...
May 11, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28446389/infectious-and-non-infectious-pulmonary-complications-in-primary-immunodeficiencies
#13
R Yazdani, H Abolhassani, M Asgardoon, M Shaghaghi, M Modaresi, G Azizi, A Aghamohammadi
Primary immunodeficiency disorders (PIDs) have been described as diseases caused by one or more defects of the immune system. These patients are more likely to experience recurrent and/or severe infections and have a tendency to develop a wide range of complications. Respiratory diseases are the main and initial manifestation for the majority of PID patients and most common complication in this group of patients. Pulmonary complications present a significant cause of morbidity and also mortality among patients suffering from different forms of PIDs...
April 27, 2017: Journal of Investigational Allergology & Clinical Immunology
https://www.readbyqxmd.com/read/28442213/pathogenic-cd4-t-cells-in-patients-with-asthma
#14
REVIEW
Lyndsey M Muehling, Monica G Lawrence, Judith A Woodfolk
Asthma encompasses a variety of clinical phenotypes that involve distinct T cell-driven inflammatory processes. Improved understanding of human T-cell biology and the influence of innate cytokines on T-cell responses at the epithelial barrier has led to new asthma paradigms. This review captures recent knowledge on pathogenic CD4(+) T cells in asthmatic patients by drawing on observations in mouse models and human disease. In patients with allergic asthma, TH2 cells promote IgE-mediated sensitization, airway hyperreactivity, and eosinophilia...
April 22, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28421631/subclinical-lower-airways-correlates-of-chronic-allergic-and-non-allergic-rhinitis
#15
Ricardo J Saranz, Alejandro Lozano, Natalia A Lozano, Marina F Ponzio, Álvaro A Cruz
The upper and lower airways behave as a physiological and pathophysiological unit. Subclinical lower airways abnormalities have been described in patients with rhinitis without asthma. These are expressed as bronchial hyperreactivity, abnormalities in lung function and bronchial inflammation, likely as a result of the same phenomenon with systemic inflammatory impact that reaches both the nose and the lungs, which for unknown reasons does not always have a full clinical expression. Patients with rhinitis are at increased risk of developing asthma; therefore most authors suggest a careful clinical evaluation and monitoring of these patients, especially if symptoms related to inflammation in the lower airways are observed...
April 19, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28385814/tnf%C3%AE-enhances-force-generation-in-airway-smooth-muscle
#16
Murat Dogan, Young-Soo Han, Philippe Delmotte, Gary C Sieck
Airway inflammation is a hallmark of asthma, triggering airway smooth muscle (ASM) hyperreactivity and airway remodeling. TNFα increases both agonist-induced cytosolic Ca(2+) concentration ([Ca(2+)]cyt) and force in ASM. The effects of TNFα on ASM force may also be due to an increase in Ca(2+) sensitivity, cytoskeletal remodeling, and/or changes in contractile protein content. We hypothesized that 24 h of exposure to TNFα increases ASM force by changing actin and myosin heavy chain (MyHC) content and/or polymerization...
June 1, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28378089/interleukin-13-increases-pendrin-abundance-to-the-cell-surface-in-bronchial-nci-h292-cells-via-rho-actin-signaling
#17
Annamaria Russo, Marianna Ranieri, Annarita Di Mise, Silvia Dossena, Tommaso Pellegrino, Emilia Furia, Charity Nofziger, Lucantonio Debellis, Markus Paulmichl, Giovanna Valenti, Grazia Tamma
Interleukin-13 (IL13) is a major player in the development of airway hyperresponsiveness in several respiratory disorders. Emerging data suggest that an increased expression of pendrin in airway epithelia is associated with elevated airway hyperreactivity in asthma. Here, we investigate the effect of IL13 on pendrin localization and function using bronchiolar NCI-H292 cells. The data obtained revealed that IL13 increases the cell surface expression of pendrin. This effect was paralleled by a significant increase in the intracellular pH, possibly via indirect stimulation of NHE...
April 4, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28370266/inhaled-steroids-reduce-pain-and-svcam-levels-in-individuals-with-sickle-cell-disease-a-triple-blind-randomized-trial
#18
Jeffrey Glassberg, Caterina Minnitti, Caroline Cromwell, Lawrence Cytryn, Thomas Kraus, Gwen S Skloot, Jason T Connor, Adeeb H Rahman, William J Meurer
Clinical and preclinical data demonstrate that altered pulmonary physiology (including increased inflammation, increased blood flow, airway resistance, and hyper-reactivity) is an intrinsic component of Sickle Cell Disease (SCD) and may contribute to excess SCD morbidity and mortality. Inhaled corticosteroids (ICS), a safe and effective therapy for pulmonary inflammation in asthma, may ameliorate the altered pulmonary physiologic milieu in SCD. With this single-center, longitudinal, randomized, triple-blind, placebo controlled trial we studied the efficacy and feasibility of ICS in 54 nonasthmatic individuals with SCD...
March 28, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28353351/effects-of-human-umbilical-cord-blood-mononuclear-cells-on-respiratory-system-mechanics-in-a-murine-model-of-neonatal-lung-injury
#19
David R Mills, Quanfu Mao, Sharon Chu, Kate Falcon Girard, Morey Kraus, James F Padbury, Monique E De Paepe
BACKGROUND: Mononuclear cells (MNCs) have well-documented beneficial effects in a wide range of adult pulmonary diseases. The effects of human umbilical cord blood-derived MNCs on neonatal lung injury, highly relevant for potential autologous application in preterm newborns at risk for bronchopulmonary dysplasia (BPD), remain incompletely established. The aim of this study was to determine the long-term morphologic and functional effects of systemically delivered MNCs in a murine model of neonatal lung injury...
March 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28275108/maternal-high-fat-diet-in-mice-leads-to-innate-airway-hyperresponsiveness-in-the-adult-offspring
#20
Kelvin D MacDonald, Aurelia R Moran, Ashley J Scherman, Cindy T McEvoy, Astrid S Platteau
Maternal obesity prior to and during pregnancy has been associated with an increased incidence of childhood asthma. As diets rich in saturated fat are linked to obesity and inflammation, we created a murine model to investigate the effect of maternal high-fat diet (HFD) on adult offspring airway hyperreactivity (AHR), a cardinal feature of asthma. Balb/cByJ dams were fed a HFD (60% fat Calories) or normal-fat diet (NFD) (10% fat Calories) from 8 weeks prior to first breeding through their pregnancies. Pups were weaned to either a HFD or NFD (at 4 weeks of age)...
March 2017: Physiological Reports
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