Epithelial cell dysfunction, a major driver of asthma development

Heijink, Irene H.; Kuchibhotla, Virinchi N. S.; Roffel, Mirjam P.; Maes, Tania; Knight, Darryl A.; Sayers, Ian; Nawijn, Martijn C.

doi:10.1111/all.14421

Cited by 184 publications

(162 citation statements)

References 161 publications

(356 reference statements)

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“…1 Accordingly, repeated injury, repair, and regeneration of the airway epithelium following exposure to environmental factors and inflammation results in histological changes and functional abnormalities in the airway mucosal epithelium, which are associated with the pathophysiology of asthma. 2 Epigenetics is defined by heritable changes in gene expression without changes in the DNA sequence. 3 Regulation of gene expression is mediated by different mechanisms such as DNA methylation, histone modifications, and RNA-associated silencing by small non-coding RNAs.…”

Section: Inhibition Of Cpg Methylation Improves the Barrier Integrity Of Bronchial Epithelial Cells In Asthmamentioning

confidence: 99%

Inhibition of CpG methylation improves the barrier integrity of bronchial epithelial cells in asthma

Krawczyk

Acharya

Tan

et al. 2020

Allergy

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Section: Inhibition Of Cpg Methylation Improves the Barrier Integrity Of Bronchial Epithelial Cells In Asthmamentioning

confidence: 99%

Inhibition of CpG methylation improves the barrier integrity of bronchial epithelial cells in asthma

Krawczyk

Acharya

Tan

et al. 2020

Allergy

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“…The interaction of HDM allergen inhalation and airway epithelial cells has been shown to directly cause airway epithelium dysfunction [36]. Due to the activation of airway epithelial cells responding to HDM allergen, a series of epithelial-derived cytokines are rapidly released, and simultaneously recruit neighboring innate and adaptive immune cells, which are essential for the pathogenesis of asthma.…”

Section: Discussionmentioning

confidence: 99%

Clara cell 16KDa protein mitigates house dust mite-induced airway inflammation and damage via regulating airway epithelial cell apoptosis in a manner dependent on HMGB1-mediated signaling inhibition.

Liu

Zhang

et al. 2021

Preprint

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Background: House dust mite (HDM) inhalation can cause airway epithelial damage which is implicated in the process of airway inflammation in asthma. High mobility group box 1 (HMGB1) is critically required for cellular damage and apoptosis as an important endogenous danger signal. Recently, Clara cell 16KDa protein (CC16) has been identified to exert anti-inflammatory and immunomodulatory influence in various injury-related diseases model. However, little is known about its ability to protect against airway epithelial injury in allergic asthma. This study was aimed to clarify the protective roles of CC16 on airway epithelia in HDM-induced asthma and the regulation of HMGB1 by CC16.Methods: Mice were sensitized and challenged by HDM extract and administrated intranasally with CC16 (5ug/g or 10ug/g) or saline in the challenged period. The BEAS-2B human airway epithelial cell line were cultured with CC16 or the control vehicle and then exposed to HDM. Knockdown or overexpression of HMGB1 was induced by cell transfection or intratracheal injection of recombinant adenovirus.Results: CC16 treatment decreased airway inflammation and histological damage of airway epithelium dose-dependently in HDM-induced asthma model. Airway epithelia apoptosis upon HDM stimulation was noticeably abrogated by CC16 in vivo and in vitro. In addition, upregulation of HMGB1 expression and its related signaling were also detected under HDM conditions, while silencing HMGB1 significantly inhibited the apoptosis of BEAS-2B cells. Furthermore, the activity of HMGB1-mediated signaling was restrained after CC16 treatment whereas HMGB1 overexpression abolished the protective effect of CC16 on HDM-induced airway epithelia apoptosis.Conclusions: Our data confirm that CC16 attenuates HDM-mediated airway inflammation and damage via suppressing airway epithelial cell apoptosis in a HMGB1-dependent manner, suggesting the role of CC16 as a potential protective option for HDM-induced asthma.

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“…One group of genes associated with asthma are related to the epithelial barrier function (see summary in ref. [ 33 ]); these include PCDH1 (protocadherin-1), which is involved in cell adhesion and epithelial barrier formation [ 34 ] and CDHR3 (cadherin-related family member 3), which is also involved in cell adhesion as well as epithelial polarity and is the receptor for rhinovirus (RV) C, where the risk variant could increase susceptibility to infection [ 35 , 36 , 37 ]. Additionally, ORMDL3 (orosomucoid-like 3) has been linked to asthma in several populations [ 38 , 39 , 40 ], and its corresponding protein may be involved in cell adhesion and integrity; when increased, it has been shown to promote airway remodeling and hyperresponsiveness [ 41 ].…”

Section: Genetic Associations With Asthma Linked To the Airway Epimentioning

confidence: 99%

The Airway Epithelium—A Central Player in Asthma Pathogenesis

Calvén

Rådinger

2020

IJMS

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Asthma is a chronic inflammatory airway disease characterized by variable airflow obstruction in response to a wide range of exogenous stimuli. The airway epithelium is the first line of defense and plays an important role in initiating host defense and controlling immune responses. Indeed, increasing evidence indicates a range of abnormalities in various aspects of epithelial barrier function in asthma. A central part of this impairment is a disruption of the airway epithelial layer, allowing inhaled substances to pass more easily into the submucosa where they may interact with immune cells. Furthermore, many of the identified susceptibility genes for asthma are expressed in the airway epithelium. This review focuses on the biology of the airway epithelium in health and its pathobiology in asthma. We will specifically discuss external triggers such as allergens, viruses and alarmins and the effect of type 2 inflammatory responses on airway epithelial function in asthma. We will also discuss epigenetic mechanisms responding to external stimuli on the level of transcriptional and posttranscriptional regulation of gene expression, as well the airway epithelium as a potential treatment target in asthma.

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Epithelial cell dysfunction, a major driver of asthma development

Cited by 184 publications

References 161 publications

Inhibition of CpG methylation improves the barrier integrity of bronchial epithelial cells in asthma

Inhibition of CpG methylation improves the barrier integrity of bronchial epithelial cells in asthma

Clara cell 16KDa protein mitigates house dust mite-induced airway inflammation and damage via regulating airway epithelial cell apoptosis in a manner dependent on HMGB1-mediated signaling inhibition.

The Airway Epithelium—A Central Player in Asthma Pathogenesis

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