Determining the Effects and Signaling Properties of β-Blockers in House Dust Mite-Driven Murine Models of Asthma
type: CreativeWork
description: Asthma is a chronic inflammatory disease of the airways affecting more than 300 million people worldwide. Some characteristic features of asthma include airway inflammation, mucus hypersecretion, airway hyper-responsiveness and remodeling causing clinical symptoms such as recurrent coughing, wheezing, chest tightness, and shortness of breath. As often patients require life-long management of these symptoms, health care costs associated with asthma management are continually increasing, particularly in developed countries such as the United States, where asthma is highly prevalent. The gold-standard drugs for asthma therapy include inhaled corticosteroids (ICS) and β2-adrenoceptor (β2AR) agonists. However, chronic monotherapy with β2AR agonists has been associated with worsening of asthma control and an increase in asthma-related mortality. Previous studies in our laboratory discovered that agonist activation of the β2AR is actually required for developing the asthma phenotype in ovalbumin-driven murine models of asthma. Furthermore, our studies suggested that chronic treatment with certain β-blockers such as nadolol and ICI 118, 551 was able to attenuate the asthma phenotype in murine models. However, not all β-blockers seemed to work as carvedilol and propranolol did not reduce the asthma phenotype in mice. Further studies in our laboratory suggested a correlation between the ability of β-blockers to reduce the asthma phenotype in murine models and their inhibition of the β2AR- associated β-arrestin-2-ERK1/2 pathway. All our previous studies were conducted in ovalbumin-driven murine models of asthma. However, ovalbumin models have been criticized for lacking clinical relevance. To address the limitations of the ovalbumin models, we tested the β-blockers carvedilol and nadolol in more clinically relevant models of asthma using the allergens from house dust mites (HDM). To further increase the clinical relevance of our present studies, we designed protocols to study …
abstract: Asthma is a chronic inflammatory disease of the airways affecting more than 300 million people worldwide. Some characteristic features of asthma include airway inflammation, mucus hypersecretion, airway hyper-responsiveness and remodeling causing clinical symptoms such as recurrent coughing, wheezing, chest tightness, and shortness of breath. As often patients require life-long management of these symptoms, health care costs associated with asthma management are continually increasing, particularly in developed countries such as the United States, where asthma is highly prevalent. The gold-standard drugs for asthma therapy include inhaled corticosteroids (ICS) and β2-adrenoceptor (β2AR) agonists. However, chronic monotherapy with β2AR agonists has been associated with worsening of asthma control and an increase in asthma-related mortality. Previous studies in our laboratory discovered that agonist activation of the β2AR is actually required for developing the asthma phenotype in ovalbumin-driven murine models of asthma. Furthermore, our studies suggested that chronic treatment with certain β-blockers such as nadolol and ICI 118, 551 was able to attenuate the asthma phenotype in murine models. However, not all β-blockers seemed to work as carvedilol and propranolol did not reduce the asthma phenotype in mice. Further studies in our laboratory suggested a correlation between the ability of β-blockers to reduce the asthma phenotype in murine models and their inhibition of the β2AR- associated β-arrestin-2-ERK1/2 pathway. All our previous studies were conducted in ovalbumin-driven murine models of asthma. However, ovalbumin models have been criticized for lacking clinical relevance. To address the limitations of the ovalbumin models, we tested the β-blockers carvedilol and nadolol in more clinically relevant models of asthma using the allergens from house dust mites (HDM). To further increase the clinical relevance of our present studies, we designed protocols to study …
author: Joshi, Radhika
language: eng
keywords: Asthma, Β-adrenoceptor blockers, House dust mites, Extracellular-signal regulated kinases 1/2, Β-arrestin-2
date published: 2017-12
date modified: 2026-07-24T02:32:24Z
provider: University of Houston
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Houston

PropertyValue
property ID: Handle
value: http://hdl.handle.net/10657/3636