Therapeutic administration of Budesonide ameliorates allergen-induced airway remodelling.
ABSTRACT Airway inflammation and remodelling are important pathophysiologic features of chronic asthma. Although current steroid use demonstrates anti-inflammatory activity, there are limited effects on the structural changes in the lung tissue.
We have used a mouse model of prolonged allergen challenge that exhibits many of the salient features of airway remodelling in order to investigate the anti-remodelling effects of Budesonide.
Treatment was administered therapeutically, with dosing starting after the onset of established eosinophilic airway inflammation and hyper-reactivity.
Budesonide administration reduced airway hyper-reactivity and leukocyte infiltration in association with a decrease in production of the Th2 mediators, IL-4, IL-13 and eotaxin-1. A reduction in peribronchiolar collagen deposition and mucus production was observed. Moreover, our data show for the first time that, Budesonide treatment regulated active transforming growth factor (TGF)-beta signalling with a reduction in the expression of pSmad 2 and the concomitant up-regulation of Smad 7 in lung tissue sections.
Therefore, we have determined that administration of Budesonide modulates the progression of airway remodelling following prolonged allergen challenge via regulation of inflammation and active TGF-beta signalling.
- SourceAvailable from: Wasu Kamchaisatian
Article: Serum TGF-beta1 in atopic asthma.[Show abstract] [Hide abstract]
ABSTRACT: Asthma is a chronic inflammatory disease of the airway. Pathological repair of chronic inflammation leads to airway remodeling. Transforming growth factor-beta (TGF-beta), a profibrotic cytokine, plays an important role in promoting the structural changes of airway remodeling. TGF-beta effects on the proliferation, differentiation and extracellular matrix (ECM) metabolism of airway structural cells. This study assessed serum TGF-beta1 in different severity of atopic asthma compared to non-atopic controls. Thirty-one atopic asthmatic patients and 34 non-atopic controls, aged 7-18 years, were recruited as to the asthma severity: steroid naïve mild asthma, moderate asthma, and asthma in remission. Serum TGF-beta1 was measured by enzyme-linked immunosorbent assay. There was a significant difference between serum TGF-beta1 in asthmatic patients and that in control patients (39.59 ng/ml vs. 0.26 ng/ml, p < 0.001). Serum TGF-beta1 was highest in steroid naïve mild asthma group when compared to the moderate asthma and asthma in remission groups (47.44 ng/ml vs. 38.64 ng/ml and 47.44 ng/ml vs. 35.94 ng/ml, p = 0.013 and 0.001, respectively). There were no correlations among serum TGF-beta1 and pulmonary function test parameters, duration of asthma, and duration of inhaled corticosteroid treatment. These data support the role of TGF-beta1 in airway remodeling in asthma.Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand 01/2009; 26(4):185-9. · 0.79 Impact Factor
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ABSTRACT: KCa3.1 has been suggested to be involved in regulating cell activation, proliferation and migration in multiple cell types including airway inflammatory and structural cells. However, the contribution of KCa3.1 to airway inflammation and remodeling and subsequent airway hyperresponsiveness (AHR) in allergic asthma remains to be explored. The main purpose of this study was to elucidate the roles of the KCa3.1 and potential therapeutic value of KCa3.1 blockers in chronic allergic asthma. Using real-time PCR, Western blot, and/or immunohistochemical analyses, we explored the precise role of KCa3.1 in bronchus of allergic mice and asthmatic human bronchial smooth muscle cells (BSMCs). We found that KCa3.1 mRNA and protein expression were elevated in the bronchus of allergic mice, and double labeling revealed that up-regulation occurred primarily in airway SMCs. TRAM-34, a KCa3.1 blocker, dose-dependently inhibited the generation and maintenance of OVA-induced airway inflammation associated with increased Th2-type cytokines and decreased Th1-type cytokine as well as subepithelial extracellular matrix deposition, goblet cell hyperplasia and AHR in mouse model of asthma. Moreover, pharmacological blockade and gene silencing of KCa3.1, which elevated evidently after mitogen stimulation, suppressed asthmatic human BSMCs proliferation and migration and arrested the cell cycle at the G0/G1 phase. Additionally, KCa3.1 activator 1-EBIO-induced membrane hyperpolarization and intracellular calcium increase in asthmatic human BSMCs were attenuated by TRAM-34. We demonstrate for the first time that an important role for KCa3.1 in the pathogenesis of airway inflammation and remodeling in allergic asthma and suggest that KCa3.1 blockers may represent a promising therapeutic strategy for asthma.American Journal of Respiratory Cell and Molecular Biology 03/2013; · 4.15 Impact Factor
- American Journal of Respiratory and Critical Care Medicine 01/2007; 174(11):1173-6; discussion 1176-8. · 11.04 Impact Factor