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Allergen asthma challenge study

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https://www.readbyqxmd.com/read/28212463/efficacy-and-tolerability-of-an-inhaled-selective-glucocorticoid-receptor-modulator-azd5423-in-copd-patients-phase-ii-study-results
#1
Piotr Kuna, Magnus Aurivillius, Carin Jorup, Susanne Prothon, Ziad Taib, Staffan Edsbäcker
AZD5423 is a novel, inhaled, selective glucocorticoid receptor modulator (SGRM), which in an allergen challenge model in asthmatics improved lung function and airway hyper-reactivity. In the current trial, AZD5423 was for the first time tested in patients with chronic obstructive pulmonary disease (COPD). In this double-blind, randomised and parallel group study, we examined airway and systemic effects of two doses of AZD5423, inhaled via Turbuhaler for 12 weeks, in 353 symptomatic COPD patients (average pre-bronchodilator forced expiratory volume in one second (FEV1) at screening was 50-52% of predicted normal)...
February 17, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28205598/lyn-regulates-mucus-secretion-and-muc5ac-via-the-stat6-signaling-pathway-during-allergic-airway-inflammation
#2
Xiaoyun Wang, Yin Li, Deyu Luo, Xing Wang, Yun Zhang, Zhigang Liu, Nanshan Zhong, Min Wu, Guoping Li
Hypersecretion of mucus is an important component of airway remodeling and contributes to the mucus plugs and airflow obstruction associated with severe asthma phenotypes. Lyn has been shown to down-regulate allergen-induced airway inflammation. However, the role of Lyn in mucin gene expression remains unresolved. In this study, we first demonstrate that Lyn overexpression decreased the mucus hypersecretion and levels of the muc5ac transcript in mice exposed to ovalbumin (OVA). Lyn overexpression also decreased the infiltration of inflammatory cells and the levels of IL-13 and IL-4 in OVA-challenged airways...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28114934/effect-of-a-retinoid-x-receptor-partial-agonist-on-airway-inflammation-and-hyperresponsiveness-in-a-murine-model-of-asthma
#3
Utako Fujii, Nobuaki Miyahara, Akihiko Taniguchi, Naohiro Oda, Daisuke Morichika, Etsuko Murakami, Hikari Nakayama, Koichi Waseda, Mikio Kataoka, Hiroki Kakuta, Mitsune Tanimoto, Arihiko Kanehiro
BACKGROUND: Retinoid X receptors (RXRs) are members of the nuclear receptor (NR) superfamily that mediate signaling by 9-cis retinoic acid, a vitamin A (retinol) derivative. RXRs play key roles not only as homodimers but also as heterodimeric partners-e.g., retinoic acid receptors (RARs), vitamin D receptors (VDRs), liver X receptors (LXRs), and peroxisome proliferator-activated receptors (PPARs). The NR family was recently associated with allergic diseases, but the role of RXRs in allergen-induced airway responses is not well defined...
January 23, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28111308/notch-signaling-in-t-cells-is-essential-for-allergic-airway-inflammation-but-expression-of-notch-ligands-jagged1-and-jagged2-on-dendritic-cells-is-dispensable
#4
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 T helper 2 (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: 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/28110885/mir-155-contributes-to-df1-induced-asthma-by-increasing-the-proliferative-response-of-th-cells-via-ctla-4-downregulation
#5
Yingying Zhang, Entao Sun, Xueqin Li, Mengying Zhang, Zongsheng Tang, Ling He, Kun Lv
Allergen-induced airway inflammation is characterized by Th2-mediated eosinophilic inflammation in the lungs. While the molecular mechanisms leading to this abnormal Th2 response remain unclear. Recent studies have demonstrated that MicroRNAs (miRNAs) modulate allergic airway inflammation. In this study, the role of miRNAs in allergic asthma pathogenesis was examined. Differentially expressed miRNAs were identified via miRNA microarray, with miR-155 being among the most highly expressed in asthma mice lungs...
January 7, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28097237/oxidized-camkii-promotes-asthma-through-the-activation-of-mast-cells
#6
Jingjing Qu, Danh C Do, Yufeng Zhou, Elizabeth Luczak, Wayne Mitzner, Mark E Anderson, Peisong Gao
Oxidation of calmodulin-dependent protein kinase II (ox-CaMKII) by ROS has been associated with asthma. However, the contribution of ox-CaMKII to the development of asthma remains to be fully characterized. Here, we tested the effect of ox-CaMKII on IgE-mediated mast cell activation in an allergen-induced mouse model of asthma using oxidant-resistant CaMKII MMVVδ knockin (MMVVδ) mice. Compared with WT mice, the allergen-challenged MMVVδ mice displayed less airway hyperresponsiveness (AHR) and inflammation...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28043871/bcl-2-inhibitors-reduce-steroid-insensitive-airway-inflammation
#7
Bao-Ping Tian, Li-Xia Xia, Zheng-Qiang Bao, Hao Zhang, Zhi-Wei Xu, Yuan-Yuan Mao, Chao Cao, Luan-Qing Che, Jin-Kai Liu, Wen Li, Zhi-Hua Chen, Songmin Ying, Hua-Hao Shen
BACKGROUND: Asthmatic inflammation is dominated by accumulation of either eosinophils, neutrophils, or both in the airways. Disposal of these inflammatory cells is the key to disease control. Eosinophilic airway inflammation is responsive to corticosteroid treatment, whereas neutrophilic inflammation is resistant and increases the burden of global health care. Corticosteroid-resistant neutrophilic asthma remains mechanistically poorly understood and requires novel effective therapeutic strategies...
December 31, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27939889/trigonella-foenum-graecum-alleviates-airway-inflammation-of-allergic-asthma-in-ovalbumin-induced-mouse-model
#8
Chun Hua Piao, Thi Tho Bui, Chang Ho Song, Hee Soon Shin, Dong-Hwa Shon, Ok Hee Chai
Trigonella foenum-graecum, a member oldest medicinal plant in the fabaceae (legumes) family, is used as a herb, spice, and vegetable, and known for its olfactory, laxative, and galactogogue effects. However, the inhibitory effect of Trigonella foenum-graecum on allergic inflammatory response remains unclear, therefore, we investigated the precise role of Trigonella foenum-graecum in the allergic asthma and revealed the effects of Trigonella foenum-graecum in regulating airway inflammation and its possible mechanism...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27891156/usefulness-of-component-resolved-analysis-of-cat-allergy-in-routine-clinical-practice
#9
Katharina Eder, Sven Becker, Marion San Nicoló, Alexander Berghaus, Moritz Gröger
BACKGROUND: Cat allergy is of great importance, and its prevalence is increasing worldwide. Cat allergens and house dust mite allergens represent the major indoor allergens; however, they are ubiquitous. Cat sensitization and allergy are known risk factors for rhinitis, bronchial hyperreactivity and asthma. Thus, the diagnosis of sensitization to cats is important for any allergist. METHODS: 70 patients with positive skin prick tests for cats were retrospectively compared regarding their skin prick test results, as well as their specific immunoglobulin E antibody profiles with regard to their responses to the native cat extract, rFel d 1, nFel d 2 and rFel d 4...
2016: Allergy, Asthma, and Clinical Immunology
https://www.readbyqxmd.com/read/27854355/effects-of-asian-dust-particles-on-the-early-stage-antigen-induced-immune-response-of-asthma-in-nc-nga-mice
#10
Jun Kurai, Masanari Watanabe, Hiroyuki Sano, Degejirihu Hantan, Yuji Tohda, Eiji Shimizu
Asian dust (AD) can aggravate airway inflammation in asthma, but the association between AD and the development of asthma remains unclear. This study aimed to investigate the effects of AD on the early stage of antigen sensitization using a mouse model of asthma, as well as the role of leukotrienes (LTs) in antigen-induced airway inflammation potentiated by AD particles. NC/Nga mice were co-sensitized by intranasal instillation of AD particles and/or Dermatophagoides farinae (Df) for five consecutive days. Df-sensitized mice were stimulated with an intranasal Df challenge at seven days...
November 16, 2016: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/27847210/targeted-inhibition-of-six1-attenuates-allergic-airway-inflammation-and-remodeling-in-asthmatic-mice
#11
Zhao-Chuan Yang, Ming-Ji Yi, Yan-Chun Shan, Chong Wang, Ni Ran, Li-Ying Jin, Peng Fu, Xue-Ying Feng, Lei Xu, Zheng-Hai Qu
Asthma is an inflammatory disease of the airways, characterized by lung eosinophilia, mucus hypersecretion by goblet cells and airway hyperresponsiveness to inhaled allergens. The purpose of this study was to evaluate the effects of Six1 on airway inflammation and remodeling and the underlying mechanisms in a murine model of chronic asthma. Female BALB/c mice were randomly divided into four groups: phosphate-buffered saline control, ovalbumin (OVA)-induced asthma group, OVA+siNC and OVA+siSix1. In this mice model, Six1 expression level was significantly elevated in OVA-induced asthma of mice...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27846830/overexpression-of-programmed-cell-death-5-in-a-mouse-model-of-ovalbumin-induced-allergic-asthma
#12
Xiaolin Diao, Juan Wang, Hong Zhu, Bei He
BACKGROUND: Programmed cell death 5 (PDCD5) was first identified as an apoptosis-promoting protein and involved in some autoimmune diseases and inflammatory processes. Our previous study demonstrated greater expression of serum PDCD5 in asthmatic patients than controls. This study aimed to further explore the significance of PDCD5 in mice with induced allergic asthma. METHODS: We divided 16 female mice into 2 groups: control (n = 8) and allergen (ovalbumin, OVA)-challenged mice (n = 8)...
November 15, 2016: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/27787629/lymphangiogenesis-in-rat-asthma-model
#13
Aigul Moldobaeva, John Jenkins, Qiong Zhong, Elizabeth M Wagner
Although bronchial angiogenesis has been well documented in allergic asthma, lymphangiogenesis has not been widely studied. Therefore, we evaluated changes in lung lymphatics in a rat model of allergen-induced asthma using house dust mite (Der p 1; 100 μg/challenge). Additionally, properties of isolated lung lymphatic endothelial cells (CD45(-), CD141(+), LYVE-1(+), Prox-1(+)) were studied in vitro. Three weeks after the onset of intranasal allergen exposure (twice-weekly), an increase in the number of lung lymphatic vessels was measured (34% increase) by lung morphometry...
February 2017: Angiogenesis
https://www.readbyqxmd.com/read/27779664/inhalation-of-inactivated%C3%A2-mycobacterium%C3%A2-phlei-prevents-asthma%C3%A2-mediated-airway-hyperresponsiveness-and-airway-eosinophilia-in-mice-by-reducing-il%C3%A2-5-and-il%C3%A2-13-levels
#14
Moyu Ming, Zhixi Luo, Shengqiu Lv, Chaoqian Li
The present study aimed to investigate whether inhalation of inactivated‑Mycobacterium phlei could prevent airway hyperresponsiveness and airway eosinophilia. A total of 24 male Balb/c mice were randomly divided into three groups: Normal control group (group A), asthma model group (group B) and the intervention group (group C), (8 mice/group). Group A mice were sensitized and with challenged saline and group B with ovalbumin (OVA). Group C mice were administered with aerosol Mycobacterium phlei once daily prior to the allergen challenge...
December 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27746238/house-dust-mite-driven-asthma-and-allergen-specific-t-cells-depend-on-b-cells-when-the-amount-of-inhaled-allergen-is-limiting
#15
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 hyperresponsiveness and eosinophilia. B cells can present antigens to CD4 T cells and produce IgE immunoglobulins that arm effector cells; however, mouse models are inconclusive on whether B cells are necessary for asthma development. OBJECTIVES: We sought to address the role of B cells in a house dust mite (HDM)-driven TH2-high asthma mouse model. METHODS: Wild-type and B cell-deficient muMT mice were sensitized and challenged through the airways with HDM extracts...
October 13, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27743410/development-of-eosinophilic-inflammation-is-independent-of-b-t-cell-interaction-in-a-chronic-house-dust-mite-driven-asthma-model
#16
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
https://www.readbyqxmd.com/read/27733553/blomia-tropicalis-specific-tcr-transgenic-th2-cells-induce-inducible-balt-and-severe-asthma-in-mice-by-an-il-4-il-13-dependent-mechanism
#17
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...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27685606/allergen-induced-increases-in-interleukin-25-and-interleukin-25-receptor-expression-in-mature-eosinophils-from-atopic-asthmatics
#18
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...
2016: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/27633092/adenovirus-mediated-foxp3-expression-in-lung-epithelial-cells-reduces-airway-inflammation-in-ovalbumin-and-cockroach-induced-asthma-model
#19
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
https://www.readbyqxmd.com/read/27602069/interstitial-collagen-turnover-during-airway-remodeling-in-acute-and-chronic-experimental-asthma
#20
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
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