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Allergen asthma challenge study

Melissa Dullaers, Martijn J Schuijs, Monique Willart, Kaat Fierens, Justine Van Moorleghem, Hamida Hammad, Bart N Lambrecht
BACKGROUND: Allergic asthma is a CD4 Th2-lymphocyte driven disease characterized by airway hyper-responsiveness and eosinophilia. B cells can present antigens to CD4 T cells and produce IgE immunoglobulins which arms effector cells, however mouse models are inconclusive whether B cells are necessary for asthma development. OBJECTIVES: To address the role of B cells in a house dust mite (HDM) driven Th2-high asthma mouse model. METHODS: WT and B cell deficient muMT Mice were sensitized and challenged via the airways with HDM extracts...
October 13, 2016: Journal of Allergy and Clinical Immunology
H Vroman, I M Bergen, B W S Li, J A C van Hulst, M Lukkes, D van Uden, R W Hendriks, M Kool
BACKGROUND: Chronic exposure to environmental triggers, such as house dust mite (HDM), drives T helper 2 (Th2) cell-mediated asthma. Recent evidence has shown that B-T cell interaction, and in particular germinal center reactions and follicular T helper (Tfh) cells are required for the development of eosinophilic airway inflammation in HDM-driven models containing a sensitization and challenge phase. Whether B-T cell interactions are essential for pulmonary eosinophilic inflammation following chronic allergen provocation remains unknown...
October 15, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Yen Leong Chua, Ka Hang Liong, Chiung-Hui Huang, Hok Sum Wong, Qian Zhou, Say Siong Ler, Yafang Tang, Chin Pei Low, Hui Yu Koh, I-Chun Kuo, Yongliang Zhang, W S Fred Wong, Hong Yong Peh, Hwee Ying Lim, Moyar Qing Ge, Angela Haczku, Veronique Angeli, Paul A MacAry, Kaw Yan Chua, David M Kemeny
Previous studies have highlighted the importance of lung-draining lymph nodes in the respiratory allergic immune response, whereas the lung parenchymal immune system has been largely neglected. We describe a new in vivo model of respiratory sensitization to Blomia tropicalis, the principal asthma allergen in the tropics, in which the immune response is focused on the lung parenchyma by transfer of Th2 cells from a novel TCR transgenic mouse, specific for the major B. tropicalis allergen Blo t 5, that targets the lung rather than the draining lymph nodes...
October 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Wei Tang, Steven G Smith, Brittany Salter, John Paul Oliveria, Patrick Mitchell, Graeme M Nusca, Karen Howie, Gail M Gauvreau, Paul M O'Byrne, Roma Sehmi
BACKGROUND: Interleukin (IL)-25 plays a pivotal role in type 2 immune responses. In a baseline cross-sectional study, we previously showed that IL-25 plasma levels and IL-25 receptor (IL-25R: IL-17RA, IL-17RB, and IL-17RA/RB) expression on mature blood eosinophils are increased in atopic asthmatics compared to normal nonatopic controls. This study investigated allergen-induced changes in IL-25 and IL-25R expression in eosinophils from asthmatics. METHODS: Dual responder atopic asthmatics (n = 14) were enrolled in this randomized diluent-controlled crossover allergen challenge study...
September 30, 2016: International Archives of Allergy and Immunology
Soojin Park, Hwan-Suck Chung, Dasom Shin, Kyung-Hwa Jung, Hyunil Lee, Junghee Moon, Hyunsu Bae
Foxp3 is a master regulator of CD4(+)CD25(+) regulatory T-cell (Treg) function and is also a suppressor of SKP2 and HER2/ErbB2. There are an increasing number of reports describing the functions of Foxp3 in cell types other than Tregs. In this context, we evaluated the functions of Foxp3 in ovalbumin- and cockroach-induced asthma models. Foxp3-EGFP-expressing adenovirus or EGFP control adenovirus was administered intratracheally (i.t.), followed by challenge with ovalbumin (OVA) or cockroach extract to induce asthma...
September 16, 2016: Experimental & Molecular Medicine
Georgina González-Avila, Blanca Bazan-Perkins, Cuauhtémoc Sandoval, Bettina Sommer, Sebastian Vadillo-Gonzalez, Carlos Ramos, Arnoldo Aquino-Galvez
Asthma airway remodeling is characterized by the thickening of the basement membrane (BM) due to an increase in extracellular matrix (ECM) deposition, which contributes to the irreversibility of airflow obstruction. Interstitial collagens are the primary ECM components to be increased during the fibrotic process. The aim of the present study was to examine the interstitial collagen turnover during the course of acute and chronic asthma, and 1 month after the last exposure to the allergen. Guinea pigs sensitized to ovalbumin (OVA) and exposed to 3 further OVA challenges (acute model) or 12 OVA challenges (chronic model) were used as asthma experimental models...
September 2016: Experimental and Therapeutic Medicine
Zeneng Wang, Joseph A DiDonato, Jennifer Buffa, Suzy A Comhair, Mark A Aronica, Raed A Dweik, Nancy A Lee, James J Lee, Mary Jane Thomassen, Mani Kavuru, Serpil C Erzurum, Stanley L Hazen
The biochemical mechanisms through which eosinophils contribute to asthma pathogenesis are unclear. Here we show eosinophil peroxidase (EPO), an abundant granule protein released by activated eosinophils, contributes to characteristic asthma-related phenotypes through oxidative posttranslational modification (PTM) of proteins in asthmatic airways through a process called carbamylation. Using a combination of studies we now show EPO uses plasma levels of the pseudohalide thiocyanate (SCN(-)) as substrate to catalyze protein carbamylation, as monitored by PTM of protein lysine residues into N(ϵ)-carbamyllysine (homocitrulline), and contributes to the pathophysiological sequelae of eosinophil activation...
October 14, 2016: Journal of Biological Chemistry
Manuel A R Ferreira, Rick Jansen, Gonneke Willemsen, Brenda Penninx, Lisa M Bain, Cristina T Vicente, Joana A Revez, Melanie C Matheson, Jennie Hui, Joyce Y Tung, Svetlana Baltic, Peter Le Souëf, Grant W Montgomery, Nicholas G Martin, Colin F Robertson, Alan James, Philip J Thompson, Dorret I Boomsma, John L Hopper, David A Hinds, Rhiannon B Werder, Simon Phipps
BACKGROUND: Hundreds of genetic variants are thought to contribute to variation in asthma risk by modulating gene expression. Methods that increase the power of genome wide association studies (GWAS) to identify risk-associated variants are needed. OBJECTIVE: To develop a method that aggregates the evidence for association with disease risk across expression quantitative trait loci (eQTLs) of a gene and use this approach to identify asthma risk genes. METHODS: We developed a gene-based test and software package called EUGENE that (1) is applicable to GWAS summary statistics; (2) considers both cis- and trans-eQTLs; (3) incorporates eQTLs identified in different tissues; and (4) uses simulations to account for multiple testing...
August 20, 2016: Journal of Allergy and Clinical Immunology
Eero Lauhkonen, Petri Koponen, Kirsi Nuolivirta, Merja Helminen, Marita Paassilta, Jyri Toikka, Matti Korppi
AIM: The united airway disease (UAD) hypothesis suggests that allergic rhinitis and asthma develop together. We evaluated the evidence for and against the UAD hypothesis at five to seven years of age after hospitalisation for bronchiolitis at less than six months. METHODS: This study used prospective follow-up data for 102 children hospitalised for bronchiolitis under the age of six months. We included the presence of previous and current asthma, prolonged rhinitis and skin prick tests (SPT) to common inhaled allergens and lung function by impulse oscillometry (IOS) at five to seven years of age...
November 2016: Acta Paediatrica
Xiao Na Ge, Sung Gil Ha, Yana G Greenberg, Amrita Rao, Idil Bastan, Ada G Blidner, Savita P Rao, Gabriel A Rabinovich, P Sriramarao
Galectin-1 (Gal-1), a glycan-binding protein with broad antiinflammatory activities, functions as a proresolving mediator in autoimmune and chronic inflammatory disorders. However, its role in allergic airway inflammation has not yet been elucidated. We evaluated the effects of Gal-1 on eosinophil function and its role in a mouse model of allergic asthma. Allergen exposure resulted in airway recruitment of Gal-1-expressing inflammatory cells, including eosinophils, as well as increased Gal-1 in extracellular spaces in the lungs...
August 16, 2016: Proceedings of the National Academy of Sciences of the United States of America
Weisong Zhou, Jian Zhang, Kasia Goleniewska, Daniel E Dulek, Shinji Toki, Dawn C Newcomb, Jacqueline Y Cephus, Robert D Collins, Pingsheng Wu, Mark R Boothby, R Stokes Peebles
Allergic airway diseases are immune disorders associated with heightened type 2 immune responses and IL-5 and IL-13 production at the site of inflammation. We have previously reported that cyclooxygenase (COX) inhibition by indomethacin augmented allergic airway inflammation in a STAT6-independent manner. However, the key COX product(s) responsible for restraining indomethacin-mediated STAT6-independent allergic inflammation is unknown. In this study, using the mouse model of OVA-induced allergic airway inflammation, we identified that PGI2 receptor (IP) signaling was critical for indomethacin-induced, STAT6-independent proallergic effects...
September 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Samir N P Kelada
Allergic asthma is common airway disease that is characterized in part by enhanced airway constriction in response to nonspecific stimuli. Genome-wide association studies have identified multiple loci associated with asthma risk in humans, but these studies have not accounted for gene-environment interactions, which are thought to be important factors in asthma. To identify quantitative trait loci (QTL) that regulate responses to a common human allergen, we applied a house dust mite mouse (HDM) model of allergic airway disease (AAD) to 146 incipient lines of the Collaborative Cross (CC) and the CC founder strains...
2016: G3: Genes—Genomes—Genetics
Gail M Gauvreau, Louis-Philippe Boulet, J Mark FitzGerald, Donald W Cockcroft, Beth E Davis, Richard Leigh, Masaya Tanaka, Jon A Fourre, Makoto Tanaka, Toshiya Nabata, Paul M O'Byrne
BACKGROUND: The cysteinyl leukotrienes (cysLTs) play a key role in the pathophysiology of asthma. In addition to functioning as potent bronchoconstrictors, cysLTs contribute to airway inflammation through eosinophil and neutrophil chemotaxis, plasma exudation and mucus secretion. We tested the activity of the dual cysLT1/2 antagonist, ONO-6950, against allergen-induced airway responses. METHODS: Subjects with documented allergen-induced early (EAR) and late asthmatic response (LAR) were randomized in a 3-way crossover study to receive ONO-6950 (200 mg) or montelukast (10 mg) or placebo q...
July 22, 2016: Allergy
Rob G J A Zuiker, Catherine Tribouley, Zuzana Diamant, J Diderik Boot, Adam F Cohen, K Van Dyck, I De Lepeleire, Veronica M Rivas, Vladislav A Malkov, Jacobus Burggraaf, Marcella K Ruddy
BACKGROUND: Inhaled allergen challenge is a validated disease model of allergic asthma offering useful pharmacodynamic assessment of pharmacotherapeutic effects in a limited number of subjects. OBJECTIVES: To evaluate whether an RNA signature can be identified from induced sputum following an inhaled allergen challenge, whether a RNA signature could be modulated by limited doses of inhaled fluticasone, and whether these gene expression profiles would correlate with the clinical endpoints measured in this study...
2016: European Clinical Respiratory Journal
Wei-Ping Zeng, Margaret M McFarland, Baohua Zhou, Silva Holtfreter, Susan Flesher, Ambrose Cheung, Avishek Mallick
BACKGROUND: TH2 responses are implicated in asthma pathobiology. Epidemiologic studies have found a positive association between asthma and exposure to staphylococcal enterotoxins. OBJECTIVE: We used a mouse model of asthma to determine whether staphylococcal enterotoxins promote TH2 differentiation of allergen-specific CD4 conventional T (Tcon) cells and asthma by activating allergen-nonspecific regulatory T (Treg) cells to create a TH2-polarizing cytokine milieu...
June 8, 2016: Journal of Allergy and Clinical Immunology
Chandler B Sy, Mark C Siracusa
Asthma is a heterogeneous disorder that results in recurrent attacks of breathlessness, coughing, and wheezing that affects millions of people worldwide. Although the precise causes of asthma are unclear, studies suggest that a combination of genetic predisposition and environmental exposure to various allergens and pathogens contribute to its development. Currently, the most common treatment to control asthma is a dual combination of β2-adrenergic receptor agonists and corticosteroids. However, studies have shown that some patients do not respond well to these medications, while others experience significant side effects...
2016: Frontiers in Physiology
D Singh, B Leaker, M Boyce, M A Nandeuil, S Collarini, F Mariotti, D Santoro, P J Barnes
CHF6001 is an inhaled phosphodiesterase 4 (PDE4) inhibitor in development for the treatment of obstructive lung diseases. The efficacy and safety of CHF6001 were investigated in a double blind, placebo controlled, 3-way cross-over study using the allergen challenge model. Thirty-six atopic asthmatics who were not taking inhaled corticosteroids and who demonstrated a late asthmatic response (LAR) to inhaled allergen at screening were randomised to receive CHF6001 400 μg or 1200 μg or placebo administered once a day using a dry powder inhaler...
October 2016: Pulmonary Pharmacology & Therapeutics
Guro Gafvelin, Jeanette Grundström, Maria Edin Grimheden, Sara Sánchez Vidaurre, Kameran Daham, Sven-Erik Dahlén, Barbro Dahlén, Marianne van Hage
BACKGROUND: Selective inhibition of cyclooxygenase-2 (COX-2) reduces the production of prostaglandin E2 (PGE2), which can have both pro- and anti-inflammatory effects on allergic inflammation. Moreover, in vitro PGE2 has been shown to affect inflammation through the modulation of lymphocyte responses. METHODS: Sixteen subjects with mild allergic asthma were recruited to a two-period cross-over study: one treatment period with the selective COX-2 inhibitor etoricoxib and one without...
2016: International Archives of Allergy and Immunology
Vaibhav Shrirang Dhawale, Venkateswara Rao Amara, Pinakin Arun Karpe, Vajir Malek, Deep Patel, Kulbhushan Tikoo
Angiotensin-I converting enzyme (ACE) is positively correlated to asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS) and is highly expressed in lungs. ACE2, the counteracting enzyme of ACE, was proven to be protective in pulmonary, cardiovascular diseases. In the present study we checked the effect of ACE2 activation in animal model of asthma. Asthma was induced in male wistar rats by sensitization and challenge with ovalbumin and then treated with ACE2 activator, diminazene aceturate (DIZE) for 2weeks...
September 1, 2016: Toxicology and Applied Pharmacology
Antonio Moreno, Fernando Pineda, Javier Alcover, David Rodríguez, Ricardo Palacios, Eduardo Martínez-Naves
PURPOSE: Hypersensitivity to fungi is associated with rhinoconjunctivitis and asthma. For some fungi, such as Alternaria alternata (A. alternata), the symptoms of asthma are persistent, increasing disease severity and the risk of fatal outcomes. There are a large number of species of fungi but knowledge of them remains limited. This, together with the difficulties in obtaining adequate standardized extracts, means that there remain significant challenges in the diagnosis and immunotherapy of allergy associated with fungi...
September 2016: Allergy, Asthma & Immunology Research
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