Airway epithelial barrier function regulates the pathogenesis of allergic asthma

Heijink, Irene H.; Nawijn, Martijn C.; Hackett, Tillie L.

doi:10.1111/cea.12296

Cited by 105 publications

(90 citation statements)

References 139 publications

(158 reference statements)

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“…The epithelial protective mechanism is crucial, with recent studies indeed challenging the existing inflammation-dominant theory of asthma pathogenesis [26,27]. Evidently, most of the available genome-wide scan studies have indicated the possibility of the governing role of the airway epithelia in determining asthmatic airway inflammation [28]. In this context, we also found no alteration of goblet cell metaplasia with PBPB treatment (fig.…”

Section: Discussionsupporting

confidence: 53%

Parabromophenacyl Bromide Inhibits Subepithelial Fibrosis by Reducing TGF-β<sub>1</sub> in a Chronic Mouse Model of Allergic Asthma

Ram

Mabalirajan²,

Jaiswal³

et al. 2015

Int Arch Allergy Immunol

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Background: Our previous study showed that parabromophenacyl bromide (PBPB) inhibits the features of allergic airway inflammation and airway hyperresponsiveness (AHR). However, its effect on airway remodeling, e.g. subepithelial ﬁbrosis in a chronic allergic asthma model, was not investigated. We examined this issue in this study. Methods: PBPB was administered to mice with an induced chronic asthmatic condition. AHR was estimated at the end of the experiment, followed by euthanasia. Lung sections were stained with hematoxylin and eosin, periodic acid-Schiff and Masson's trichrome to determine airway inflammation, goblet cell metaplasia and subepithelial fibrosis, respectively. Transforming growth factor-β₁ (TGF-β₁) was estimated in lung homogenates. To determine the effect of PBPB on smooth-muscle hyperplasia, immunohistochemistry against α-smooth-muscle actin was performed on the lung sections. Results: Chronic ovalbumin challenges in a mouse model of allergic asthma caused significant subepithelial ﬁbrosis and elevated TGF-β₁, along with significant AHR. PBPB attenuated subepithelial ﬁbrosis with a reduction of lung TGF-β₁, airway inflammation and AHR without affecting goblet cell metaplasia. It also attenuated smooth-muscle hyperplasia with a reduction in the expression of α-smooth-muscle actin in the lungs. Conclusion: Our findings indicate that PBPB attenuates some crucial features of airway remodeling such as subepithelial ﬁbrosis and smooth-muscle hyperplasia. These data suggest that PBPB could therefore be a therapeutic drug for chronic asthma.

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Section: Discussionsupporting

confidence: 53%

Parabromophenacyl Bromide Inhibits Subepithelial Fibrosis by Reducing TGF-β<sub>1</sub> in a Chronic Mouse Model of Allergic Asthma

Ram

Mabalirajan²,

Jaiswal³

et al. 2015

Int Arch Allergy Immunol

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“…The bronchial epithelium is increasingly recognised as a critical airway cell involved in the pathogenesis and persistence of asthma [59]. This is highlighted by the altered function of the epithelium in patients with asthma compared with those without [60].…”

Section: Bronchial Epitheliummentioning

confidence: 99%

Novel concepts in airway inflammation and remodelling in asthma

2015

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The hallmark pathological features of asthma include airway eosinophilic inflammation and structural changes (remodelling) which are associated with an irreversible loss in lung function that tracks from childhood to adulthood. In parallel with changes in function, pathological abnormalities occur early, during the pre-school years, are established by school age and subsequently remain (even though symptoms may remit for periods during adulthood). Given the equal importance of inflammation and remodelling in asthma pathogenesis, there is a significant disparity in studies undertaken to investigate the contribution of each. The majority focus on the role of inflammation, and although novel therapeutics such as those targeted against T-helper cell type 2 (Th2) mediators have arisen, it is apparent that targeting inflammation alone has not allowed disease modification. Therefore, unless airway remodelling is addressed for future therapeutic strategies, it is unlikely that we will progress towards a cure for asthma. Having acknowledged these limitations, the focus of this review is to highlight the gaps in our current knowledge about the mechanisms underlying airway remodelling, the relationships between remodelling, inflammation and function, remodelling and clinical phenotypes, and the importance of utilising innovative and realistic pre-clinical models to uncover effective, disease-modifying therapeutic strategies. @ERSpublications We discuss mechanisms of airway inflammation and remodelling in asthma to uncover effective therapeutic strategies http://ow.ly/SsXiO

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“…Reduced epithelial integrity or enhanced epithelial fragility has been put forward as a common cause for allergic disorders (Heijink et al, 2014), and increased release of these two cytokines upon epithelial challenge might be a hallmark of susceptibility to these diseases. This characteristic of allergic disease also identifies these two cytokines as key targets for future intervention.…”

Section: Genetic and Clinical Evidence For The Role Of Il-33 And Tslpmentioning

confidence: 99%

IL-33 and Thymic Stromal Lymphopoietin in mast cell functions

Saluja

Zoltowska

Ketelaar

et al. 2016

European Journal of Pharmacology

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Airway epithelial barrier function regulates the pathogenesis of allergic asthma

Cited by 105 publications

References 139 publications

Parabromophenacyl Bromide Inhibits Subepithelial Fibrosis by Reducing TGF-β<sub>1</sub> in a Chronic Mouse Model of Allergic Asthma

Parabromophenacyl Bromide Inhibits Subepithelial Fibrosis by Reducing TGF-β<sub>1</sub> in a Chronic Mouse Model of Allergic Asthma

Novel concepts in airway inflammation and remodelling in asthma

IL-33 and Thymic Stromal Lymphopoietin in mast cell functions

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