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Hyperreactive Airway

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https://www.readbyqxmd.com/read/28515358/irf5-distinguishes-severe-asthma-in-humans-and-drives-th1-phenotype-and-airway-hyperreactivity-in-mice
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
Murat Dogan, Young-Soo Han, Philippe F 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 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 exposure TNFα increases ASM force by changing actin and myosin heavy chain (MyHC) content and/or polymerization. Porcine ASM strips were permeabilized with 10% Triton X-100, and force was measured in response to increasing concentrations of Ca(2+) (pCa 9...
April 6, 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
#8
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
#9
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 hyperreactivity) is an intrinsic component of 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 non-asthmatic 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
#10
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
#11
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
https://www.readbyqxmd.com/read/28258108/newly-divided-eosinophils-limit-ozone-induced-airway-hyperreactivity-in-non-sensitized-guinea-pigs
#12
Sarah Anne Wicher, David B Jacoby, Allison D Fryer
Ozone causes vagally-mediated airway hyperreactivity and recruits inflammatory cells, including eosinophils, to lungs where they mediate ozone-induced hyperreactivity one day after exposure, but are paradoxically protective three days later. To test the role of newly divided eosinophils in ozone-induced airway hyperreactivity in sensitized and non-sensitized guinea pigs. Non-sensitized and sensitized guinea pigs were treated with 5-bromo-2-deoxyuridine (BrdU) to label newly divided cells and were exposed to air or ozone for 4 hours...
March 3, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28223414/the-flavonoid-cyanidin-blocks-binding-of-the-cytokine-interleukin-17a-to-the-il-17ra-subunit-to-alleviate-inflammation-in-vivo
#13
Caini Liu, Liang Zhu, Koichi Fukuda, Suidong Ouyang, Xing Chen, Chenhui Wang, Cun-Jin Zhang, Bradley Martin, Chunfang Gu, Luke Qin, Suguna Rachakonda, Mark Aronica, Jun Qin, Xiaoxia Li
Cyanidin, a key flavonoid that is present in red berries and other fruits, attenuates the development of several diseases, including asthma, diabetes, atherosclerosis, and cancer, through its anti-inflammatory effects. We investigated the molecular basis of cyanidin action. Through a structure-based search for small molecules that inhibit signaling by the proinflammatory cytokine interleukin-17A (IL-17A), we found that cyanidin specifically recognizes an IL-17A binding site in the IL-17A receptor subunit (IL-17RA) and inhibits the IL-17A/IL-17RA interaction...
February 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28194433/mitochondrial-camkii-inhibition-in-airway-epithelium-protects-against-allergic-asthma
#14
Sara C Sebag, Olha M Koval, John D Paschke, Christopher J Winters, Omar A Jaffer, Ryszard Dworski, Fayyaz S Sutterwala, Mark E Anderson, Isabella M Grumbach
Excessive ROS promote allergic asthma, a condition characterized by airway inflammation, eosinophilic inflammation, and increased airway hyperreactivity (AHR). The mechanisms by which airway ROS are increased and the relationship between increased airway ROS and disease phenotypes are incompletely defined. Mitochondria are an important source of cellular ROS production, and our group discovered that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is present in mitochondria and activated by oxidation...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28178290/prenatal-exposure-to-respiratory-syncytial-virus-alters-postnatal-immunity-and-airway-smooth-muscle-contractility-during-early-life-reinfections
#15
Paul M Brown, Terri J Harford, Vandana Agrawal, Belinda Yen-Lieberman, Fariba Rezaee, Giovanni Piedimonte
Maternal viral infections can have pathological effects on the developing fetus which last long after birth. Recently, maternal-fetal transmission of respiratory syncytial virus (RSV) was shown to cause postnatal airway hyperreactivity (AHR) during primary early-life reinfection; however, the influence of prenatal exposure to RSV on offspring airway immunity and smooth muscle contractility during recurrent postnatal reinfections remains unknown. Therefore, we sought to determine whether maternal RSV infection impairs specific aspects of cell-mediated offspring immunity during early-life reinfections and the mechanisms leading to AHR...
2017: PloS One
https://www.readbyqxmd.com/read/28174048/the-effects-of-particulate-matter-on-inflammation-of-respiratory-system-differences-between-male-and-female
#16
Kelly Yoshizaki, Jôse Mára Brito, Luiz Fernando Silva, Adriana Lino-Dos-Santos-Franco, Daniela Perroni Frias, Renata Calciolari Rossi E Silva, Luís Fernando Amato-Lourenço, Paulo Hilário Nascimento Saldiva, Iolanda de Fátima Lopes Calvo Tibério, Thais Mauad, Mariangela Macchione
Air pollution is known to exacerbate respiratory diseases and epidemiological studies have shown that women present more chronic respiratory symptoms than man exposed to traffic pollution, however, the reason why is unclear. This study evaluated the inflammatory differences in BALB/c mouse males (n=34) and females (n=111) in three phases of the estrous cycle that were exposed to ambient air (AA) or concentrated ambient particles (CAPs). Tracheal hyperreactivity to methacholine, bronchoalveolar lavage fluid (BALF) and immunohistochemical of airways and lung parenchyma were studied...
May 15, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28160290/regulatory-t-cells-and-type-2-innate-lymphoid-cell-dependent-asthma
#17
REVIEW
J L Aron, O Akbari
Group 2 innate lymphoid cells (ILC2s) are a recently identified group of cells with the potent capability to produce Th2-type cytokines such as interleukin (IL)-5 and IL-13. Several studies suggest that ILC2s play an important role in the development of allergic diseases and asthma. Activation of pulmonary ILC2s in murine models lacking T and B cells induces eosinophilia and airway hyper-reactivity (AHR), which are cardinal features of asthma. More importantly, numerous recent studies have highlighted the role of ILC2s in asthma persistence and exacerbation among human subjects, and thus, regulation of pulmonary ILC2s is a major area of investigation aimed at curbing allergic lung inflammation and exacerbation...
February 4, 2017: Allergy
https://www.readbyqxmd.com/read/28140833/nanoparticles-induced-apoptosis-of-human-airway-epithelium-is-mediated-by-prongf-p75-ntr-signaling
#18
Sreeparna Chakraborty, Vincent Castranova, Miriam K Perez, Giovanni Piedimonte
Environmental and occupational exposures to respirable ultrafine fractions of particulate matter (PM) have been implicated in the initiation and exacerbation of lung diseases. However, the precise mechanisms underlying production of cell damage and death attributed to nanoparticles (NP) on human airway epithelium are not fully understood. This study examined the role of neurotrophic pathways in NP-induced airway toxicity. Size and agglomeration of TiO2 nanoparticles (TiO2-NP) and fine (TiO2-FP) particles were measured by dynamic light scattering...
2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28111308/notch-signaling-in-t-cells-is-essential-for-allergic-airway-inflammation-but-expression-of-the-notch-ligands-jagged-1-and-jagged-2-on-dendritic-cells-is-dispensable
#19
Irma Tindemans, Melanie Lukkes, Marjolein J W de Bruijn, Bobby W S Li, Menno van Nimwegen, Derk Amsen, Alex KleinJan, Rudi W Hendriks
BACKGROUND: Allergic asthma is characterized by a TH2 response induced by dendritic cells (DCs) that present inhaled allergen. Although the mechanisms by which they instruct TH2 differentiation are still poorly understood, expression of the Notch ligand Jagged on DCs has been implicated in this process. OBJECTIVE: We sought to establish whether Notch signaling induced by DCs is critical for house dust mite (HDM)-driven allergic airway inflammation (AAI) in vivo...
January 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28091773/the-nervous-system-of-airways-and-its-remodeling-in-inflammatory-lung-diseases
#20
REVIEW
Katrin Julia Audrit, Lucas Delventhal, Öznur Aydin, Christina Nassenstein
Inflammatory lung diseases are associated with bronchospasm, cough, dyspnea and airway hyperreactivity. The majority of these symptoms cannot be primarily explained by immune cell infiltration. Evidence has been provided that vagal efferent and afferent neurons play a pivotal role in this regard. Their functions can be altered by inflammatory mediators that induce long-lasting changes in vagal nerve activity and gene expression in both peripheral and central neurons, providing new targets for treatment of pulmonary inflammatory diseases...
March 2017: Cell and Tissue Research
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