The mixture of siRNAs targeted to IL-4 and IL-13 genes effectively reduces the airway hyperreactivity and allergic inflammation in a mouse model of asthma

2022 ◽  
Vol 103 ◽  
pp. 108432
Author(s):  
Shilovskiy IP ◽  
Sundukova MS ◽  
Korneev AV ◽  
Nikolskii AA ◽  
Barvinskaya ED ◽  
...  
Keyword(s):  
Mouse Model ◽  
Allergic Inflammation ◽  
Airway Hyperreactivity

The Mixture of siRNAs Targeted to IL-4 and IL-13 Genes Effectively Reduces the Airway Hyperreactivity and Allergic Inflammation in a Mouse Model of Asthma

2021 ◽  
Author(s):  
Igor Shilovskiy ◽  
Maria Sundukova ◽  
A.A Nikolskii ◽  
Ekaterina Barvinskaya ◽  
V Kovchina ◽  
...  
Keyword(s):  
Mouse Model ◽  
Allergic Inflammation ◽  
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 Disulfide disruption reverses mucus dysfunction in allergic airway disease

2019 ◽  
Author(s):  
Leslie E. Morgan ◽  
Siddharth K. Shenoy ◽  
Dorota Raclawska ◽  
Nkechinyere A. Emezienna ◽  
Vanessa L. Richardson ◽  
...  
Keyword(s):  
Disulfide Bonds ◽  
Allergic Inflammation ◽  
Airway Disease ◽  
Airway Hyperreactivity ◽  
Allergic Airway Disease ◽  
Mucus Hypersecretion ◽  
Asthma Model ◽  
Targeted Treatments ◽  
Fungal Allergen ◽  
Respiratory Conditions

Airway mucus is essential for healthy lung defense1, but excessive mucus in asthma obstructs airflow, leading to severe and potentially fatal outcomes2–5. Current asthma therapies reduce allergic inflammation and relax airway smooth muscle, but treatments are often inadequate due to their minimal effects on mucus obstruction6,7. The lack of efficacious mucus-targeted treatments stems from a poor understanding of healthy mucus function and pathological mucus dysfunction at a molecular level. The chief macromolecules in mucus, polymeric mucins, are massive glycoproteins whose sizes and biophysical properties are dictated in part by covalent disulfide bonds that link mucin molecules into assemblies of 10 or more subunits8. Once secreted, mucin glycopolymers can aggregate to form plugs that block airflow. Here we show that reducing mucin disulfide bonds depolymerizes mucus in human asthma and reverses pathological effects of mucus hypersecretion in a mouse allergic asthma model. In mice challenged with a fungal allergen, inhaled mucolytic treatment acutely loosened mucus mesh, enhanced mucociliary clearance (MCC), and abolished airway hyperreactivity (AHR) to the bronchoprovocative agent methacholine. AHR reversal was directly related to reduced mucus plugging. Furthermore, protection in mucolytic treated mice was identical to prevention observed in mice lacking Muc5ac, the polymeric mucin required for allergic AHR in murine models9. These findings establish grounds for developing novel fast-acting agents to treat mucus hypersecretion in asthma10,11. Efficacious mucolytic therapies could be used to directly improve airflow, help resolve inflammation, and enhance the effects of inhaled treatments for asthma and other respiratory conditions11,12.

Inhibition of MicroRNA-21 by an antagomir ameliorates allergic inflammation in a mouse model of asthma

2017 ◽  
Vol 43 (3) ◽  
pp. 109-119 ◽  
Author(s):  
Hwa Young Lee ◽  
Hea Yon Lee ◽  
Joon Young Choi ◽  
Jung Hur ◽  
In Kyoung Kim ◽  
...  
Keyword(s):  
Mouse Model ◽  
Allergic Inflammation

Blocking ATP releasing channels prevents high extracellular ATP levels and airway hyperreactivity in an asthmatic mouse model

2021 ◽  
Author(s):  
Llilian Arzola Martínez ◽  
Rebeca Benavente ◽  
Génesis Vega ◽  
Mariana Ríos ◽  
Wendy Fonseca ◽  
...  
Keyword(s):  
Mouse Model ◽  
Airway Inflammation ◽  
Airway Epithelium ◽  
Atp Release ◽  
Specific Inhibitor ◽  
Extracellular Atp ◽  
Airway Hyperreactivity ◽  
Luciferase Assay ◽  
Asthmatic Patients ◽  
Allergic Mouse

Allergic asthma is a chronic airway inflammatory response to different triggers like inhaled allergens. Excessive ATP in fluids from asthmatic patients is considered an inflammatory signal and an important autocrine/paracrine modulator of airway physiology. Here we investigated the deleterious effect of increased extracellular ATP (eATP) concentration on the mucociliary clearance (MCC) effectiveness and determined the role of ATP releasing channels during airway inflammation in an ovalbumin (OVA)-sensitized mouse model. Our allergic mouse model exhibited high levels of eATP measured in the tracheal fluid with a luciferin-luciferase assay and reduced MCC velocity determined by microspheres tracking in the trachea ex vivo. Addition of ATP had a dual effect on MCC, where lower ATP concentration (µM) increased microspheres velocity, while higher concentration (mM) transiently stopped microspheres movement. Also, an augmented ethidium bromide uptake by the allergic tracheal airway epithelium suggests an increase in ATP release channel functionality during inflammatory conditions. The use of carbenoxolone, a non-specific inhibitor of connexin and pannexin1channels reduced the eATP concentration in the allergic mouse tracheal fluid and dye uptake by the airway epithelium, providing evidence that these ATP release channels are facilitating the net flux of ATP to the lumen during airway inflammation. However, only the specific inhibition of pannexin1 with 10Panx peptide significantly reduced eATP in bronchoalveolar lavage and decreased airway hyperresponsiveness in OVA-allergic mouse model. These data provide evidence that blocking eATP may be a pharmacological alternative to be explored in rescue therapy during episodes of airflow restriction in asthmatic patients.

scholarly journals High dose vitamin D3 empowers effects of subcutaneous immunotherapy in a grass pollen-driven mouse model of asthma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Laura Hesse ◽  
N. van Ieperen ◽  
Arjen H. Petersen ◽  
J. N. G. Oude Elberink ◽  
Antoon J. M. van Oosterhout ◽  
...  
Keyword(s):  
Mouse Model ◽  
Grass Pollen ◽  
Airway Hyperresponsiveness ◽  
Allergic Inflammation ◽  
Optimal Dose ◽  
Lavage Fluid ◽  
Subcutaneous Immunotherapy ◽  
High Dose ◽  
Allergen Specific Immunotherapy ◽  
Neutralizing Capacity

AbstractAllergen-specific immunotherapy (AIT) has the potential to provide long-term protection against allergic diseases. However, efficacy of AIT is suboptimal, while application of high doses allergen has safety concerns. The use of adjuvants, like 1,25(OH)2VitD3 (VitD3), can improve efficacy of AIT. We have previously shown that low dose VitD3 can enhance suppression of airway inflammation, but not airway hyperresponsiveness in a grass pollen (GP)-subcutaneous immunotherapy (SCIT) mouse model of allergic asthma. We here aim to determine the optimal dose and formulation of VitD3 for the GP SCIT. GP-sensitized BALBc/ByJ mice received three SCIT injections of VitD3-GP (30, 100, and 300 ng or placebo). Separately, synthetic lipids, SAINT, was added to the VitD3-GP-SCIT formulation (300 nmol) and control groups. Subsequently, mice were challenged with intranasal GP, and airway hyperresponsiveness, GP-specific IgE, -IgG1, and -IgG2a, ear-swelling responses (ESR), eosinophils in broncho-alveolar lavage fluid and lung were measured. VitD3 supplementation of GP-SCIT dose-dependently induced significantly enhanced suppression of spIgE, inflammation and hyperresponsiveness, while neutralizing capacity was improved and ESR were reduced. Addition of VitD3 further decreased Th2 cytokine responses and innate cytokines to allergens in lung tissue by GP-SCIT. However, addition of synthetic lipids to the allergen/VitD3 mixes had no additional effect on VitD3-GP-SCIT. We find a clear, dose dependent effect of VitD3 on GP-SCIT-mediated suppression of allergic inflammation and airway hyperresponsiveness. In contrast, addition of synthetic lipids to the allergen/VitD3 mix had no therapeutic effect. These studies underscore the relevance of VitD3 as an adjuvant to improve clinical efficacy of SCIT treatment regimens.

scholarly journals Flt-3 Ligand Reverses Late Allergic Response and Airway Hyper-Responsiveness in a Mouse Model of Allergic Inflammation

2004 ◽  
Vol 172 (8) ◽  
pp. 5016-5023 ◽  
Author(s):  
Jehad H. Edwan ◽  
Greg Perry ◽  
James E. Talmadge ◽  
Devendra K. Agrawal
Keyword(s):  
Mouse Model ◽  
Allergic Inflammation ◽  
Allergic Response

Inhaled Carbenoxolone Prevents Allergic Airway Inflammation and Airway Hyperreactivity in a Mouse Model of Asthma

2008 ◽  
Vol 149 (1) ◽  
pp. 38-46 ◽  
Author(s):  
Arjun Ram ◽  
Shashi Kant Singh ◽  
Vijay Pal Singh ◽  
Sarvesh Kumar ◽  
Balaram Ghosh
Keyword(s):  
Mouse Model ◽  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Airway Hyperreactivity

scholarly journals IRAK-M Regulates Airway Hyperreactivity in a Novel Model of Ozone Induced Allergic Inflammation

2020 ◽  
Author(s):  
K. Ho ◽  
D. Herman ◽  
S. Chung ◽  
R. Thomas-Beckett ◽  
D. Weimar ◽  
...  
Keyword(s):  
Allergic Inflammation ◽  
Airway Hyperreactivity ◽  
Novel Model
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