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

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

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.

scholarly journals Autophagy Modulators From Chinese Herbal Medicines: Mechanisms and Therapeutic Potentials for Asthma

2021 ◽  
Vol 12 ◽  
Author(s):  
Yun Zhang ◽  
Xing Wang ◽  
He Zhang ◽  
Hongmei Tang ◽  
Hang Hu ◽  
...  
Keyword(s):  
Inhaled Corticosteroids ◽  
Treatment Options ◽  
Herbal Medicines ◽  
Allergic Inflammation ◽  
Gain Control ◽  
Airway Hyperreactivity ◽  
Therapeutic Interventions ◽  
Chinese Herbal ◽  
Increased Risk ◽  
Long Acting

Asthma has become a global health issue, suffering more than 300 million people in the world, which is a heterogeneous disease, usually characterized by chronic airway inflammation and airway hyperreactivity. Combination of inhaled corticosteroids (ICS) and long acting β-agonists (LABA) can relieve asthma symptoms and reduce the frequency of exacerbations, especially for patients with refractory asthma, but there are limited treatment options for people who do not gain control on combination ICS/LABA. The increase in ICS dose generally provides little additional benefit, and there is an increased risk of side effects. Therefore, therapeutic interventions integrating the use of different agents that focus on different targets are needed to overcome this set of diseases. Some findings suggest autophagy is closely correlated with the severity of asthma through eosinophilic inflammation, and its modulation may provide novel therapeutic approaches for severe allergic asthma. The chinese herbal medicine (CHM) have been demonstrated clinically as potent therapeutic interventions for asthma. Moreover some reports have found that the bioactive components isolated from CHM could modulate autophagy, and exhibit potent Anti-inflammatory activity. These findings have implied the potential for CHMs in asthma or allergic inflammation therapy via the modulation of autophagy. In this review, we discuss the basic pathomechanisms underpinning asthma, and the potential role of CHMs in treating asthma with modulating autophagy.

scholarly journals A novel mast cell-dependent allergic peritonitis model

2021 ◽  
Author(s):  
Hadas Pahima ◽  
Pier Giorgio Puzzovio ◽  
Francesca Levi-Schaffer
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Aluminum Hydroxide ◽  
Time Course ◽  
Allergic Inflammation ◽  
Trypan Blue Exclusion ◽  
Disease Characteristics ◽  
Enterotoxin B ◽  
Novel Model ◽  
Peritonitis Model

Background: Typical murine models of allergic inflammation are induced by the combination of ovalbumin and aluminum hydroxide. However, accumulating evidence indicates that, in models of asthma and atopic dermatitis, allergic inflammation can be generated in the absence of aluminum hydroxide. Moreover, co-administration of S. aureus enterotoxin B with ovalbumin can enhance inflammation. Objective: The objective of this study was to establish a rapid and mast cell-dependent murine model of allergic inflammation by inducing allergic peritonitis using ovalbumin and S. aureus enterotoxin B. Methods: Allergic peritonitis was induced in C57BL/6 mice by subcutaneous sensitization and intraperitoneal challenge with ovalbumin and S. aureus enterotoxin B. Disease characteristics were assessed by flow cytometry, ELISA, Trypan Blue exclusion and colorimetric assays. Results: Time course of the allergic peritonitis revealed a peak of peritoneal inflammation 48h after challenge, as assessed by total cells and eosinophil counts. Decrease of cell numbers started 96h post challenge with complete clearance within 168h. Moreover, significantly higher levels of tryptase and increased vascular permeability were found 30 min following challenge. Allergic inflammation induction by ovalbumin and S. aureus enterotoxin B was impaired in mast cells deficient mice and partially restored by mice reconstitution with bone marrow derived mast cells, indicating the mast cell role in this model. Conclusion: We present a novel model of allergic peritonitis that is mast cell-dependent, simple and robust. Moreover, the use of S. aureus enterotoxin B better resembles human allergic inflammation, which is known to be characterized by the colonization of Staphylococcus aureus.

scholarly journals Germinal Center Formation and Local Immunoglobulin E (IgE) Production in the Lung after an Airway Antigenic Challenge

1996 ◽  
Vol 184 (6) ◽  
pp. 2353-2360 ◽  
Author(s):  
Yolande Chvatchko ◽  
Marie H. Kosco-Vilbois ◽  
Suzanne Herren ◽  
Jean Lefort ◽  
Jean-Yves Bonnefoy
Keyword(s):  
Plasma Membranes ◽  
Plasma Cells ◽  
Immunoglobulin E ◽  
Allergic Inflammation ◽  
Cell Number ◽  
Germinal Centers ◽  
Airway Hyperreactivity ◽  
Local Source ◽  
Control Group

Airway inflammation plays a central role in the pathogenesis of asthma. However, the precise contribution of all cell types in the development and maintenance of airway hyperreactivity and histopathology during allergic inflammation remains unclear. After sensitization of mice in the periphery, challenge by multiple intratracheal (i.t.) instillations of ovalbumin (OVA) results in eosinophilia, mononuclear cell infiltration, and airway epithelial changes analogous to that seen in asthma (Blyth, D.I., M.S. Pedrick, T.J. Savage, E.M. Hessel, and D. Fattah. 1996. Am. J. Respir. Cell Mol. Biol. 14:425–438). To investigate further the nature of the cellular infiltrate, lungs from OVA-versus saline-treated mice were processed for histology and immunohistochemistry. One of the most striking features observed was the formation of germinal centers within the parenchyma of the inflamed lungs. In addition, follicular dendritic cells (FDCs) bearing OVA on their plasma membranes appeared and, adjacent to these sites, OVA-specific IgG1-, IgE-, and IgA-producing plasma cells emerged. To confirm that antigen-specific immunoglobulins (Ig) were being produced within the parenchyma, plasma cell number and antibody production were quantitated in vitro after isolation of cells from the lung. These assays confirmed that the isotypes observed in situ were a secreted product. As IgE-dependent mechanisms have been implicated as being central to the pathogenesis of bronchial asthma, airway hyperresponsiveness was evaluated. The mice undergoing lung inflammation were hyperresponsive, while the control group remained at baseline. These data demonstrate that antigen-driven differentiation of B cells via induction of an FDC network and germinal centers occurs in the parenchyma of inflamed lungs. These germinal centers would then provide a local source of IgEsecreting plasma cells that contribute to the release of factors mediating inflammatory processes in the lung.

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.

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