Deficiency Of The Bradykinin Receptor 2 (B2R) Enhances Allergic Airway Disease In A Murine OVA Asthma Model

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.

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Peptide and non-peptide bradykinin receptor antagonists: Role in allergic airway disease

European Journal of Pharmacology ◽

10.1016/j.ejphar.2005.12.071 ◽

2006 ◽

Vol 533 (1-3) ◽

pp. 215-221 ◽

Cited By ~ 34

Author(s):

William M. Abraham ◽

Mario Scuri ◽

Stephen G. Farmer

Keyword(s):

Airway Disease ◽

Allergic Airway Disease ◽

Receptor Antagonists ◽

Bradykinin Receptor

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Effect of Lavandula dentata extract on Ovalbumin-induced Asthma in Male Guinea Pigs

Brazilian Journal of Biology ◽

10.1590/1519-6984.191485 ◽

2020 ◽

Vol 80 (1) ◽

pp. 87-96

Author(s):

Z. N. Almohawes ◽

H. S. Alruhaimi

Keyword(s):

Oxidative Stress ◽

Total Cholesterol ◽

Tween 80 ◽

Airway Disease ◽

Allergic Airway Disease ◽

Adult Males ◽

Sod Activity ◽

Glucose Levels ◽

Asthma Model ◽

Guinea Pig Model

Abstract Asthma is an inflammatory disease of the lungs, and it causes oxidative stress. Lavandula dentata is an aromatic herb with anti-oxidative and anti-inflammatory activities. This study examined the activity of L. dentata extract on a guinea pig model of asthma. Adult males were divided into five groups: First group was control, second was asthma model induced by OVA, third was treated with L. dentata extract orally (300 mg/kg) for 21 days; the fourth was an asthma model with L. dentata extract (300 mg/kg) and fifth was treated with Tween 80 for 21 days. OVA treatment increased IgE, triglycerides, total cholesterol, glucose levels in serum, WBC count in blood and MDA in lungs. Also, OVA reduced SOD activity, GSH content in lungs, and GGT activity in serum (p<0.05). L. dentata extract treatment in asthma model reduced elevated IgE, triglycerides, total cholesterol, glucose levels in serum, and MDA in lungs (p<0.05), while it increased GSH content in lungs (p<0.05). These results suggest the possibility that L . dentata extract can exert suppressive effects on asthma, and may provide evidence that it is a useful agent for the treatment of allergic airway disease, it also limits oxidative stress induced by OVA. L. dentata extract appears to have hypolipidemic and hypoglycemic activities.

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