Oxidative Stress Attenuates TLR3 Responsiveness and Impairs Anti-viral Mechanisms in Bronchial Epithelial Cells From COPD and Asthma Patients

Menzel, Mandy; Ramu, Sangeetha; Calvén, Jenny; Olejnicka, Beata; Sverrild, Asger; Porsbjerg, Celeste; Tufvesson, Ellen; Bjermer, Leif; Akbarshahi, Hamid; Uller, Lena

doi:10.3389/fimmu.2019.02765

Cited by 36 publications

(32 citation statements)

References 51 publications

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“…The objective of this study is therefore to investigate the effects of constant antiviral response activation due to incomplete viral clearance toward the motile ciliary formation and assembly in the nasal epithelium during re-epithelization following infection. This will enable us to establish the association between long-term effects of impaired viral clearance and ciliary impairment in perpetuating the symptoms of chronic airway inflammatory diseases ( Bryche et al, 2019 ; Menzel et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Host Antiviral Response Suppresses Ciliogenesis and Motile Ciliary Functions in the Nasal Epithelium

Chen

Tan

Liu

et al. 2020

Front. Cell Dev. Biol.

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BackgroundRespiratory viral infections are one of the main drivers of development and exacerbation for chronic airway inflammatory diseases. Increased viral susceptibility and impaired mucociliary clearance are often associated with chronic airway inflammatory diseases and served as risk factors of exacerbations. However, the links between viral susceptibility, viral clearance, and impaired mucociliary functions are unclear. Therefore, the objective of this study is to provide the insights into the effects of improper clearance of respiratory viruses from the epithelium following infection, and their resulting persistent activation of antiviral response, on mucociliary functions.MethodsIn order to investigate the effects of persistent antiviral responses triggered by viral components from improper clearance on cilia formation and function, we established an in vitro air–liquid interface (ALI) culture of human nasal epithelial cells (hNECs) and used Poly(I:C) as a surrogate of viral components to simulate their effects toward re-epithelization and mucociliary functions of the nasal epithelium following damages from a viral infection.ResultsThrough previous and current viral infection expression data, we found that respiratory viral infection of hNECs downregulated motile cilia gene expression. We then further tested the effects of antiviral response activation on the differentiation of hNECs using Poly(I:C) stimulation on differentiating human nasal epithelial stem/progenitor cells (hNESPCs). Using this model, we observed reduced ciliated cell differentiation compared to goblet cells, reduced protein and mRNA in ciliogenesis-associated markers, and increased mis-assembly and mis-localization of ciliary protein DNAH5 following treatment with 25 μg/ml Poly(I:C) in differentiating hNECs. Additionally, the cilia length and ciliary beat frequency (CBF) were also decreased, which suggest impairment of ciliary function as well.ConclusionOur results suggest that the impairments of ciliogenesis and ciliary function in hNECs may be triggered by specific expression of host antiviral response genes during re-epithelization of the nasal epithelium following viral infection. This event may in turn drive the development and exacerbation of chronic airway inflammatory diseases.

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Section: Introductionmentioning

confidence: 99%

Host Antiviral Response Suppresses Ciliogenesis and Motile Ciliary Functions in the Nasal Epithelium

Chen

Tan

Liu

et al. 2020

Front. Cell Dev. Biol.

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“…Asthmatic mouse models and in vitro cellular experiments showed that allergens or inflammatory cytokines could stimulate airway epithelial cell activation, which increased chemokine release, attracted inflammatory immune cell infiltration into the lungs, and induced ROS production in tracheal epithelial cells [8,50]. Animal experiments also showed that these inflamed immune cells released high levels of inflammatory mediators in the lungs and induced oxidative stress, which damaged lung cells and attenuated lung function [51,52]. In the present study, we found that sesamol inhibited ROS production in inflammatory BEAS-2B cells and reduced CCL11 and CCL24 expression, which inhibited eosinophil infiltration.…”

Section: Discussionmentioning

confidence: 99%

Sesamol Alleviates Airway Hyperresponsiveness and Oxidative Stress in Asthmatic Mice

Liou

Chen

et al. 2020

Antioxidants

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Sesamol, isolated from sesame seeds (Sesamum indicum), was previously shown to have antioxidative, anti-inflammatory, and anti-tumor effects. Sesamol also inhibited lipopolysaccharide (LPS)-induced pulmonary inflammatory response in rats. However, it remains unclear how sesamol regulates airway inflammation and oxidative stress in asthmatic mice. This study aimed to investigate the efficacy of sesamol on oxidative stress and airway inflammation in asthmatic mice and tracheal epithelial cells. BALB/c mice were sensitized with ovalbumin, and received oral sesamol on days 14 to 27. Furthermore, BEAS-2B human bronchial epithelial cells were treated with sesamol to investigate inflammatory cytokine levels and oxidative responses in vitro. Our results demonstrated that oral sesamol administration significantly suppressed eosinophil infiltration in the lung, airway hyperresponsiveness, and T helper 2 cell-associated (Th2) cytokine expressions in bronchoalveolar lavage fluid and the lungs. Sesamol also significantly increased glutathione expression and reduced malondialdehyde levels in the lungs of asthmatic mice. We also found that sesamol significantly reduced proinflammatory cytokine levels and eotaxin in inflammatory BEAS-2B cells. Moreover, sesamol alleviated reactive oxygen species formation, and suppressed intercellular cell adhesion molecule-1 (ICAM-1) expression, which reduced monocyte cell adherence. We demonstrated that sesamol showed potential as a therapeutic agent for improving asthma.

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“…DExD/H-Box Helicase 58 (DDX58), also known as reticonic acid induced gene I (RIG-I), activates and regulates the expression of various in ammatory factors, thereby initiating innate and speci c immune responses 20 . Many studies have shown that RIG-I plays an important role in the in ammatory response of asthma induced by viruses [21][22][23] . Human leukocyte antigen (HLA) is a gene complex closely related to human immune function.…”

Section: Discussionmentioning

confidence: 99%

Significance of Immune-related Genes in the Diagnosis and Subtype Classification of Childhood Asthma

Dai

Sun

Cai

et al. 2020

Preprint

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Background Childhood asthma is one of the most common causes of hospitalization in children, causing huge economic losses worldwide. The immune system was closely linked to the occurrence and development of childhood asthma. The main purpose of this research is to explore the role of immune-related genes in the occurrence and treatment of childhood asthma.Methods GSE40732 dataset and GSE40888 dataset were respectively regarded as training dataset and texting dataset in this article. We performed weighted gene co-expression network analysis (WGCNA) to select immune-related genes associated with the occurrence of childhood asthma based on the training dataset. Random forest (RF) model was established to screen the optimal variables to predict the occurrence of childhood asthma among these significant immune-related genes. Childhood asthma patients were grouped by the consensus clustering method based on the optimal variables. The grouping results were validated in the texting dataset. Results 69 significant immune-related genes associated with the occurrence of childhood asthma were screened through WGCNA. RF model indicated that 10 optimal variables among these significant immune-related genes can reasonably distinguish normal children and childhood asthma. Childhood asthma patients were classified into two molecular subtypes (Sub1 and Sub2) based on the 10 optimal variables using consensus clustering analysis. More interestingly, childhood asthma patients in Sub1 have higher inflammatory response than Sub2.Conclusions Our research selected 10 significant immune-related genes related to the occurrence of childhood asthma. We classified childhood asthma patients into two molecular subtypes with different immune cell infiltration based on the 10 significant immune-related genes, which may provide the basis for individualized treatment.

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Oxidative Stress Attenuates TLR3 Responsiveness and Impairs Anti-viral Mechanisms in Bronchial Epithelial Cells From COPD and Asthma Patients

Cited by 36 publications

References 51 publications

Host Antiviral Response Suppresses Ciliogenesis and Motile Ciliary Functions in the Nasal Epithelium

Host Antiviral Response Suppresses Ciliogenesis and Motile Ciliary Functions in the Nasal Epithelium

Sesamol Alleviates Airway Hyperresponsiveness and Oxidative Stress in Asthmatic Mice

Significance of Immune-related Genes in the Diagnosis and Subtype Classification of Childhood Asthma

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