scholarly journals ADAM33 Is Not Essential for Growth and Development and Does Not Modulate Allergic Asthma in Mice

2006 ◽  
Vol 26 (18) ◽  
pp. 6950-6956 ◽  
Author(s):  
Chun Chen ◽  
Xiaozhu Huang ◽  
Dean Sheppard
Keyword(s):  
Animal Model ◽  
Allergic Asthma ◽  
Growth And Development ◽  
Immunoglobulin E ◽  
Susceptibility Gene ◽  
Airway Hyperreactivity ◽  
Mammalian Development ◽  
Asthma Susceptibility ◽  
Integrin Ligand ◽  
Mucus Metaplasia

ABSTRACT A disintegrin and metalloprotease 33 (ADAM33) is a transmembrane protease and integrin ligand that has been identified as an asthma susceptibility gene product. To determine whether ADAM33 plays important roles in mammalian development and the modulation of allergic airway dysfunction, we generated ADAM33-null mice by gene targeting. ADAM33-null mice were born at expected Mendelian ratios, and both male and females developed normally and were fertile. No anatomical or histological abnormalities were detected in any tissues. In an animal model of allergic asthma, ADAM33-null mice showed normal allergen-induced airway hyperreactivity, immunoglobulin E production, mucus metaplasia, and airway inflammation. Our results demonstrate that ADAM33 is not essential for growth or reproduction in the mouse and does not modulate baseline or allergen-induced airway responsiveness.

scholarly journals Development of Allergic Inflammation in a Murine Model of Asthma Is Dependent on the Costimulatory Receptor Ox40

2001 ◽  
Vol 193 (3) ◽  
pp. 387-392 ◽  
Author(s):  
Amha Gebre-Hiwot Jember ◽  
Riaz Zuberi ◽  
Fu-Tong Liu ◽  
Michael Croft
Keyword(s):  
T Cells ◽  
Allergic Asthma ◽  
Cd4 T Cells ◽  
Immunoglobulin E ◽  
Tumor Necrosis Factor Receptor ◽  
Allergic Inflammation ◽  
Airway Hyperreactivity ◽  
Th2 Response ◽  
Cell Hyperplasia ◽  
Mucus Production

Asthma is thought to result from an abnormal expansion of CD4 T cells reactive with airborne allergens, and pathology is controlled by several cytokines of the T helper type 2 (Th2) family. The exact molecules which are involved in generating allergen-reactive T cells are not clear. Studies with blocking reagents or knockout animals have shown that the CD28/B7 interaction partially controls development of allergic asthma in mouse models, but may not be the sole molecule involved. In this report, we have investigated the role of the tumor necrosis factor receptor family member OX40 in allergic inflammation using OX40-deficient mice. OX40 has been shown to participate in regulating clonal expansion and memory development of CD4 T cells and may synergize with CD28. Our studies demonstrate that OX40−/− mice, primed with the model allergen ovalbumin and challenged through the airways with aerosolized antigen, are severely impaired in their ability to generate a Th2 response characterized by high levels of interleukin (IL)-5, IL-4, and immunoglobulin E. Moreover, OX40−/− mice exhibit diminished lung inflammation, including an 80–90% reduction in eosinophilia and mucus production, less goblet cell hyperplasia, and significantly attenuated airway hyperreactivity. These studies highlight the potential importance of OX40 in development of allergic asthma and suggest that targeting OX40 may prove useful therapeutically.

An animal model to study the mechanisms of airway hyperreactivity associated with bronchial asthma

1990 ◽  
Vol 22 ◽  
pp. 169
Author(s):  
G.U. Di Maria ◽  
S. Bellofiore ◽  
A. Vitanza ◽  
N. Ciancio ◽  
S. Sapienza ◽  
...  
Keyword(s):  
Animal Model ◽  
Bronchial Asthma ◽  
Airway Hyperreactivity

scholarly journals Smooth muscle brain‐derived neurotrophic factor contributes to airway hyperreactivity in a mouse model of allergic asthma

2018 ◽  
Vol 33 (2) ◽  
pp. 3024-3034 ◽  
Author(s):  
Rodney D. Britt ◽  
Michael A. Thompson ◽  
Sarah A. Wicher ◽  
Logan J. Manlove ◽  
Anne Roesler ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Mouse Model ◽  
Allergic Asthma ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Airway Hyperreactivity

scholarly journals Protective effects of combined Mycobacterium bovis BCG and interleukin-12 vaccination on airway inflammation in a murine model of allergic asthma

2010 ◽  
Vol 33 (3) ◽  
pp. 196 ◽  
Author(s):  
Xia Ke ◽  
Jiangju Huang ◽  
Quan Chen ◽  
Suling Hong ◽  
Daoyin Zhu
Keyword(s):  
Airway Inflammation ◽  
Allergic Asthma ◽  
Mycobacterium Bovis ◽  
Immunoglobulin E ◽  
Allergic Airway Inflammation ◽  
Interleukin 12 ◽  
Protective Effects ◽  
Th2 Response ◽  
Bcg Vaccination ◽  
Th2 Responses

Purpose. Allergic asthma is characterized by chronic airway inflammation and airway hyperresponsiveness driven by allergen-specific T helper (Th)2 cells. Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination has been documented to suppress Th2 responses and allergic airway inflammation in animal models. Since interleukin (IL)-12 is capable of inhibiting Th2 responses, we sought to investigate whether IL-12 could function as an adjuvant to increase the efficacy of BCG vaccination against allergic asthma. Methods. BALB/c neonatal mice (24 mice, 48-72 h old) were randomly divided into 3 subgroups (n = 8 for each group) to be immunized with PBS (control) or BCG with or without DNA plasmid-expressing IL-12. All of the mice were then sensitized and provoked with ovalbumin (OVA) to establish a model of allergic asthma. Results. Mice vaccinated with BCG alone showed a significant reduction in airway inflammation, percentage of eosinophils in bronchoalveolar lavage (BAL) fluid, and serum OVA-specific immunoglobulin E (IgE) levels in comparison with control animals. The suppressive effects of BCG were substantially augmented by the combination with IL-12. Furthermore, a decreased IL-4 and increased interferon-gamma (IFN-γ) production in BAL fluid were observed in animals inoculated with BCG alone or with IL-12 relative to control animals. Conclusion. Our data indicate that the combined vaccination with BCG and IL-12 yields a favorable outcome in prevention of experimental allergic airway inflammation, which is likely mediated through triggering a shift from a Th2 response to a Th1 response.

scholarly journals Hypergravity enhances the therapeutic effect of dexamethasone in allergic asthma and rhinitis animal model

PLoS ONE ◽  
2018 ◽  
Vol 13 (5) ◽  
pp. e0197594 ◽  
Author(s):  
Tae Young Jang ◽  
Ah-Yeoun Jung ◽  
Soonjo Kwon ◽  
Young Hyo Kim
Keyword(s):  
Animal Model ◽  
Allergic Asthma ◽  
Therapeutic Effect

scholarly journals Functional Invariant NKT Cells in Pig Lungs Regulate the Airway Hyperreactivity: A Potential Animal Model

2010 ◽  
Vol 31 (2) ◽  
pp. 228-239 ◽  
Author(s):  
Gourapura J. Renukaradhya ◽  
Cordelia Manickam ◽  
Mahesh Khatri ◽  
Abdul Rauf ◽  
Xiangming Li ◽  
...  
Keyword(s):  
Animal Model ◽  
Nkt Cells ◽  
Airway Hyperreactivity ◽  
Invariant Nkt Cells

Preclinical Safety and Pharmacology of an Anti-Human Interleukin-13 Monoclonal Antibody in Normal Macaques and in Macaques with Allergic Asthma

2008 ◽  
Vol 27 (5) ◽  
pp. 351-358 ◽  
Author(s):  
Pauline L. Martin ◽  
Dusti Fisher ◽  
William Glass ◽  
Karyn O’Neil ◽  
Anuk Das ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Allergic Asthma ◽  
Immunoglobulin E ◽  
Cynomolgus Macaque ◽  
Lavage Fluid ◽  
Antigen Challenge ◽  
Interleukin 13 ◽  
Lung Eosinophilia

Interleukin-13 (IL-13) plays a central role in chronic airway diseases, including asthma. These studies were conducted to evaluate the safety of administration of a human anti-IL-13 monoclonal antibody (mAb) to normal macaques and in macaques with allergic asthma. In addition, serum and bronchioalveolar lavage fluid were collected from allergic cynomolgus macaques in order to identify potential surrogate markers of IL-13 pharmacology that could be useful for subsequent clinical trials. In vitro studies demonstrated that the anti-IL-13 mAb inhibited the pharmacological actions of both human and cynomolgus macaque IL-13. Allergic macaques were treated systemically with 10 mg/kg anti-IL-13 mAb 1 day prior to inhaled Ascaris suum antigen challenge. Normal macaques were dosed intravenously with anti-IL-13 once per week for 3 weeks at doses of 10 or 50 mg/kg. Treatment of macaques with the anti-IL-13 mAb was not associated with any toxicologically significant findings. A slight treatment-related but nonadverse decrease in platelet counts was observed in both the normal and allergic macaques. In allergic macaques, the anti-IL-13 mAb treatment did not affect lung function, lung eosinophilia, or serum or BAL immunoglobulin E (IgE) concentrations but did produce a reduction in BAL and serum eotaxin concentrations ( p < .05) at 6 h post antigen challenge. This study shows that administration of an anti-IL-13 mAb was well tolerated in both normal and allergic asthmatic macaques and that serum eotaxin concentrations may be a useful early in vivo marker for evaluating IL-13 inhibition in patients with asthma.

scholarly journals Increased Expression of CCN2 in the Red Flashing Light-Induced Myopia in Guinea Pigs

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Hong Wang ◽  
Kang Zhuang ◽  
Lei Gao ◽  
Linna Zhang ◽  
Hongling Yang
Keyword(s):  
Gene Expression ◽  
Animal Model ◽  
Axial Length ◽  
Growth And Development ◽  
Visual Environment ◽  
Biological Processes ◽  
Cellular Functions ◽  
Ocular Growth ◽  
Flashing Light

Visual environment plays an important role in the occurrence of myopia. We previously showed that the different flashing lights could result in distinct effects on the ocular growth and development of myopia. CCN2 has been reported to regulate various cellular functions and biological processes. However, whether CCN2 signaling was involved in the red flashing light-induced myopia still remains unknown. In the present study, we investigated the effects of the red flashing lights exposure on the refraction and axial length of the eyesin vivoand then evaluated their effects on the expression of CCN2 and TGF-βin sclera tissues. Our data showed that the eyes exposed to the red flashing light became more myopic with a significant increase of the axial length and decrease of the refraction. Both CCN2 and TGF-β, as well as p38 MAPK and PI3K, were highly expressed in the sclera tissues exposed to the red flashing light. Both CCN2 and TGF-βwere found to have the same gene expression profilein vivo. In conclusion, our findings found that CCN2 signaling pathway plays an important role in the red flashing light-induced myopiain vivo. Moreover, our study establishes a useful animal model for experimental myopia research.

Effectiveness and Safety Studies of Omalizumab in Children and Adolescents With Moderate-To-Severe Asthma

2021 ◽  
pp. 089719002110382
Author(s):  
Lu Cheng ◽  
Tianrui Yang ◽  
Xiang Ma ◽  
Yuling Han ◽  
Yongtai Wang
Keyword(s):  
Children And Adolescents ◽  
Allergic Asthma ◽  
Severe Asthma ◽  
Fixed Effects ◽  
Vital Capacity ◽  
Immunoglobulin E ◽  
Meta Analysis ◽  
Fixed Effects Model ◽  
Significant Difference ◽  
Severe Allergic Asthma

Background Omalizumab is currently approved for the treatment of moderate-to-severe allergic asthma in patients 6 years and older. Objective To assess the effectiveness and safety of subcutaneous omalizumab as an add-on therapy option for moderate–severe allergic asthma in patients aged 6—20 years old. Methods The studies published from July, 1970 to May, 2021 were searched from the electronic databases which followed keywords: (“anti-IgE” OR “anti-immunoglobulin E” OR “anti-IgE antibody” OR “omalizumab” OR “rhuMAb-E25” OR “Xolair”) AND “asthma” AND (“child” OR “children” OR “adolescents” OR “youth” OR “teenager” OR “kids” OR “pediatric”). Thirteen studies were pooled to determine the effectiveness and safety of omalizumab. Efficacy endpoints were evaluated using a fixed-effects model or a random-effects model depending on heterogeneity. Safety endpoints were evaluated by odds ratio. Results Thirteen studies were included. In this meta-analysis, our results showed that fractional exhaled nitric oxide and asthma control test scores were significantly improved with omalizumab treatment. Serum immunoglobulin E was also decreased in children with moderate-to-severe asthma after treatment with omalizumab. The analysis found that there was no significant difference between pre-and post-treatment in forced expiratory volume in one second/ forced vital capacity ratio, forced expiratory flow between 25 and 75% of vital capacity, or FEV1. Overall, more adverse events occurred with omalizumab compared to placebo. However, the degree was mild to moderate. Conclusion This meta-analysis indicates that omalizumab is safe and effective to treat children and adolescents with moderate-to-severe asthma.

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