scholarly journals The Airway Epithelium—A Central Player in Asthma Pathogenesis

2020 ◽  
Vol 21 (23) ◽  
pp. 8907
Author(s):  
Jenny Calvén ◽  
Elisabeth Ax ◽  
Madeleine Rådinger
Keyword(s):  
Airway Epithelium ◽  
Posttranscriptional Regulation ◽  
Inflammatory Responses ◽  
Regulation Of Gene Expression ◽  
Airflow Obstruction ◽  
Airway Disease ◽  
Airway Epithelial ◽  
Epithelial Barrier Function ◽  
Wide Range ◽  
External Stimuli

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.

scholarly journals Somatic cell hemoglobin modulates nitrogen oxide metabolism in the human airway epithelium

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nadzeya Marozkina ◽  
Laura Smith ◽  
Yi Zhao ◽  
Joe Zein ◽  
James F. Chmiel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Nitrogen Oxides ◽  
Airway Epithelium ◽  
Airflow Obstruction ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Human Airway ◽  
Human Airway Epithelium ◽  
Human Airway Epithelial Cells

AbstractEndothelial hemoglobin (Hb)α regulates endothelial nitric oxide synthase (eNOS) biochemistry. We hypothesized that Hb could also be expressed and biochemically active in the ciliated human airway epithelium. Primary human airway epithelial cells, cultured at air–liquid interface (ALI), were obtained by clinical airway brushings or from explanted lungs. Human airway Hb mRNA data were from publically available databases; or from RT-PCR. Hb proteins were identified by immunoprecipitation, immunoblot, immunohistochemistry, immunofluorescence and liquid chromatography- mass spectrometry. Viral vectors were used to alter Hbβ expression. Heme and nitrogen oxides were measured colorimetrically. Hb mRNA was expressed in human ciliated epithelial cells. Heme proteins (Hbα, β, and δ) were detected in ALI cultures by several methods. Higher levels of airway epithelial Hbβ gene expression were associated with lower FEV1 in asthma. Both Hbβ knockdown and overexpression affected cell morphology. Hbβ and eNOS were apically colocalized. Binding heme with CO decreased extracellular accumulation of nitrogen oxides. Human airway epithelial cells express Hb. Higher levels of Hbβ gene expression were associated with airflow obstruction. Hbβ and eNOS were colocalized in ciliated cells, and heme affected oxidation of the NOS product. Epithelial Hb expression may be relevant to human airways diseases.

scholarly journals The innate immune function of airway epithelial cells in inflammatory lung disease

2015 ◽  
Vol 45 (4) ◽  
pp. 1150-1162 ◽  
Author(s):  
Pieter S. Hiemstra ◽  
Paul B. McCray ◽  
Robert Bals
Keyword(s):  
Immune Responses ◽  
Airway Epithelium ◽  
Cell Function ◽  
Developmental Regulation ◽  
Airway Epithelial Cells ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Tissue Remodelling ◽  
Wide Range ◽  
Differentiation Pathways

The airway epithelium is now considered to be central to the orchestration of pulmonary inflammatory and immune responses, and is also key to tissue remodelling. It acts as the first barrier in the defence against a wide range of inhaled challenges, and is critically involved in the regulation of both innate and adaptive immune responses to these challenges. Recent progress in our understanding of the developmental regulation of this tissue, the differentiation pathways, recognition of pathogens and antimicrobial responses is now exploited to help understand how epithelial cell function and dysfunction contributes to the pathogenesis of a variety of inflammatory lung diseases. Herein, advances in our knowledge of the biology of airway epithelium, as well as its role and (dys)function in asthma, chronic obstructive pulmonary fibrosis and cystic fibrosis will be discussed.

scholarly journals Human airway lineages derived from pluripotent stem cells reveal the epithelial responses to SARS-CoV-2 infection

2022 ◽  
Author(s):  
Ruobing Wang ◽  
Adam J. Hume ◽  
Mary Lou Beermann ◽  
Chantelle Simone-Roach ◽  
Jonathan Lindstrom-Vautrin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Airway Epithelium ◽  
Disease Modeling ◽  
Inflammatory Responses ◽  
Cell Types ◽  
Severe Illness ◽  
Airway Epithelial ◽  
Airway Cells

There is an urgent need to understand how SARS-CoV-2 infects the airway epithelium and in a subset of individuals leads to severe illness or death. Induced pluripotent stem cells (iPSCs) provide a near limitless supply of human cells that can be differentiated into cell types of interest, including airway epithelium, for disease modeling. We present a human iPSC-derived airway epithelial platform, composed of the major airway epithelial cell types, that is permissive to SARS-CoV-2 infection. Subsets of iPSC-airway cells express the SARS-CoV-2 entry factors ACE2 and TMPRSS2. Multiciliated cells are the primary initial target of SARS-CoV-2 infection. Upon infection with SARS-CoV-2, iPSC-airway cells generate robust interferon and inflammatory responses and treatment with remdesivir or camostat methylate causes a decrease in viral propagation and entry, respectively. In conclusion, iPSC-derived airway cells provide a physiologically relevant in vitro model system to interrogate the pathogenesis of, and develop treatment strategies for, COVID-19 pneumonia.

scholarly journals Human airway lineages derived from pluripotent stem cells reveal the epithelial responses to SARS-CoV-2 infection

2021 ◽  
Author(s):  
Ruobing Wang ◽  
Adam Hume ◽  
Mary Lou Beermann ◽  
Chantelle Simone-Roach ◽  
Jonathan Lindstrom-Vautrin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Airway Epithelium ◽  
Disease Modeling ◽  
Inflammatory Responses ◽  
Cell Types ◽  
Severe Illness ◽  
Airway Epithelial ◽  
Airway Cells

There is an urgent need to understand how SARS-CoV-2 infects the airway epithelium and in a subset of individuals leads to severe illness or death. Induced pluripotent stem cells (iPSCs) provide a near limitless supply of human cells that can be differentiated into cell types of interest, including airway epithelium, for disease modeling. We present a human iPSC-derived airway epithelial platform, composed of the major airway epithelial cell types, that is permissive to SARS-CoV-2 infection. Subsets of iPSC-airway cells express the SARS-CoV-2 entry factors ACE2 and TMPRSS2. Multiciliated cells are the primary initial target of SARS-CoV-2 infection. Upon infection with SARS-CoV-2, iPSC-airway cells generate robust interferon and inflammatory responses and treatment with remdesivir or camostat methylate causes a decrease in viral propagation and entry, respectively. In conclusion, iPSC-derived airway cells provide a physiologically relevant in vitro model system to interrogate the pathogenesis of, and develop treatment strategies for, COVID-19 pneumonia.

scholarly journals RNA Recognition and Immunity—Innate Immune Sensing and Its Posttranscriptional Regulation Mechanisms

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1701
Author(s):  
Takuya Uehata ◽  
Osamu Takeuchi
Keyword(s):  
Nuclear Export ◽  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Inflammatory Responses ◽  
Rna Binding Proteins ◽  
Mammalian Species ◽  
Regulation Of Gene Expression ◽  
Innate Immune ◽  
Type I ◽  
Immune Sensing

RNA acts as an immunostimulatory molecule in the innate immune system to activate nucleic acid sensors. It functions as an intermediate, conveying genetic information to control inflammatory responses. A key mechanism for RNA sensing is discriminating self from non-self nucleic acids to initiate antiviral responses reliably, including the expression of type I interferon (IFN) and IFN-stimulated genes. Another important aspect of the RNA-mediated inflammatory response is posttranscriptional regulation of gene expression, where RNA-binding proteins (RBPs) have essential roles in various RNA metabolisms, including splicing, nuclear export, modification, and translation and mRNA degradation. Recent evidence suggests that the control of mRNA stability is closely involved in signal transduction and orchestrates immune responses. In this study, we review the current understanding of how RNA is sensed by host RNA sensing machinery and discuss self/non-self-discrimination in innate immunity focusing on mammalian species. Finally, we discuss how posttranscriptional regulation by RBPs shape immune reactions.

scholarly journals Airway epithelial-targeted nanoparticles for asthma therapy

2020 ◽  
Vol 318 (3) ◽  
pp. L500-L509 ◽  
Author(s):  
Stanislav Kan ◽  
Dewi Melani Hariyadi ◽  
Christopher Grainge ◽  
Darryl A. Knight ◽  
Nathan W. Bartlett ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Epithelial Cells ◽  
Airway Epithelium ◽  
Airflow Obstruction ◽  
Airway Epithelial Cells ◽  
Therapeutic Interventions ◽  
Asthma Therapy ◽  
Airway Epithelial ◽  
Management Options ◽  
Number Of Patients

Asthma is a common chronic inflammatory disease associated with intermittent airflow obstruction caused by airway inflammation, mucus overproduction, and bronchial hyperresponsiveness. Despite current treatment and management options, a large number of patients with asthma still have poorly controlled disease and are susceptible to acute exacerbations, usually caused by a respiratory virus infection. As a result, there remains a need for novel therapies to achieve better control and prevent/treat exacerbations. Nanoparticles (NPs), including extracellular vesicles (EV) and their synthetic counterparts, have been developed for drug delivery in respiratory diseases. In the case of asthma, where airway epithelium dysfunction, including dysregulated differentiation of epithelial cells, impaired barrier, and immune response, is a driver of disease, targeting airway epithelial cells with NPs may offer opportunities to repair or reverse these dysfunctions with therapeutic interventions. EVs possess multiple advantages for airway epithelial targeting, such as their natural intrinsic cell-targeting properties and low immunogenicity. Synthetic NPs can be coated with muco-inert polymers to overcome biological barriers such as mucus and the phagocytic response of immune cells. Targeting ligands could be also added to enhance targeting specificity to epithelial cells. The review presents current understanding and advances in NP-mediated drug delivery to airway epithelium for asthma therapy. Future perspectives in this therapeutic strategy will also be discussed, including the development of novel formulations and physiologically relevant preclinical models.

scholarly journals Butyrate Shapes Immune Cell Fate and Function in Allergic Asthma

2021 ◽  
Vol 12 ◽  
Author(s):  
William Yip ◽  
Michael R. Hughes ◽  
Yicong Li ◽  
Alissa Cait ◽  
Martin Hirst ◽  
...  
Keyword(s):  
Allergic Asthma ◽  
Cell Fate ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Regulation Of Gene Expression ◽  
Airway Disease ◽  
Short Chain Fatty Acids ◽  
Allergic Airway Disease ◽  
Intestinal Microbiome ◽  
And Function

The microbiome plays a fundamental role in how the immune system develops and how inflammatory responses are shaped and regulated. The “gut-lung axis” is a relatively new term that highlights a crucial biological crosstalk between the intestinal microbiome and lung. A growing body of literature suggests that dysbiosis, perturbation of the gut microbiome, is a driving force behind the development, and severity of allergic asthma. Animal models have given researchers new insights into how gut microbe-derived components and metabolites, such as short-chain fatty acids (SCFAs), influence the development of asthma. While the full understanding of how SCFAs influence allergic airway disease remains obscure, a recurring theme of epigenetic regulation of gene expression in several immune cell compartments is emerging. This review will address our current understanding of how SCFAs, and specifically butyrate, orchestrates cell behavior, and epigenetic changes and will provide a detailed overview of the effects of these modifications on immune cells in the context of allergic airway disease.

scholarly journals Airway Epithelium Dysfunction in Cystic Fibrosis and COPD

2018 ◽  
Vol 2018 ◽  
pp. 1-20 ◽  
Author(s):  
Virginia De Rose ◽  
Kevin Molloy ◽  
Sophie Gohy ◽  
Charles Pilette ◽  
Catherine M. Greene
Keyword(s):  
Cystic Fibrosis ◽  
Airway Epithelium ◽  
Critical Role ◽  
Airflow Obstruction ◽  
Alveolar Epithelium ◽  
Airway Epithelial Cells ◽  
Lung Damage ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Epithelial Dysfunction

Cystic fibrosis is a genetic disease caused by mutations in the CFTR gene, whereas chronic obstructive pulmonary disease (COPD) is mainly caused by environmental factors (mostly cigarette smoking) on a genetically susceptible background. Although the etiology and pathogenesis of these diseases are different, both are associated with progressive airflow obstruction, airway neutrophilic inflammation, and recurrent exacerbations, suggesting common mechanisms. The airway epithelium plays a crucial role in maintaining normal airway functions. Major molecular and morphologic changes occur in the airway epithelium in both CF and COPD, and growing evidence suggests that airway epithelial dysfunction is involved in disease initiation and progression in both diseases. Structural and functional abnormalities in both airway and alveolar epithelium have a relevant impact on alteration of host defences, immune/inflammatory response, and the repair process leading to progressive lung damage and impaired lung function. In this review, we address the evidence for a critical role of dysfunctional airway epithelial cells in chronic airway inflammation and remodelling in CF and COPD, highlighting the common mechanisms involved in the epithelial dysfunction as well as the similarities and differences of the two diseases.

PRMdb: A Repository of Predicted RNA Modifications in Plants

2020 ◽  
Vol 61 (6) ◽  
pp. 1213-1222
Author(s):  
Xuan Ma ◽  
Fuyan Si ◽  
Xiaonan Liu ◽  
Weijiang Luan
Keyword(s):  
Plant Species ◽  
Posttranscriptional Regulation ◽  
Regulation Of Gene Expression ◽  
Rna Modification ◽  
Rna Seq ◽  
Rna Modifications ◽  
High Throughput Analysis ◽  
Functional Studies ◽  
Web Resource ◽  
Wide Range

Abstract Evidence is mounting that RNA modifications play essential roles in posttranscriptional regulation of gene expression. So far, over 150 RNA modifications catalyzed by distinct enzymes have been documented. In plants, genome-wide identification of RNA modifications is largely limited to the model species Arabidopsis thaliana, while lacking in diverse non-model plants. Here, we present PRMdb, a plant RNA modification database, based on the analysis of thousands of RNA-seq, degradome-seq and small RNA-seq data from a wide range of plant species using the well-documented tool HAMR (high-throughput analysis of modified ribonucleotide). PRMdb provides a user-friendly interface that enables easy browsing and searching of the tRNA and mRNA modification data. We show that PRMdb collects high-confidence RNA modifications including novel RNA modification sites that can be validated by genomic PCR and reverse transcription PCR. In summary, PRMdb provides a valuable web resource for deciphering the epitranscriptomes in diverse plant species and will facilitate functional studies of RNA modifications in plants. RPMdb is available via http://www.biosequencing.cn/PRMdb/.

New Ultrastructural Observations on Injury and Regeneration of Cilia in Mammalian Conducting Airway Epithelium

1981 ◽  
Vol 39 ◽  
pp. 624-625
Author(s):  
J.L. Carson ◽  
A.M. Collier
Keyword(s):  
Respiratory Tract ◽  
Airway Epithelium ◽  
Defense Mechanisms ◽  
Normal Growth ◽  
Fetal Lung ◽  
Secretory Cells ◽  
Airway Epithelial ◽  
Ciliated Cells ◽  
Conducting Airway ◽  
Conducting Airways

The ciliated cells lining the conducting airways of mammals are integral to the defense mechanisms of the respiratory tract, functioning in coordination with secretory cells in the removal of inhaled and cellular debris. The effects of various infectious and toxic agents on the structure and function of airway epithelial cell cilia have been studied in our laboratory, both of which have been shown to affect ciliary ultrastructure.These observations have led to questions about ciliary regeneration as well as the possible induction of ciliogenesis in response to cellular injury. Classical models of ciliogenesis in the conducting airway epithelium of the mammalian respiratory tract have been based primarily on observations of the developing fetal lung. These observations provide a plausible explanation for the embryological generation of ciliary beds lining the conducting airways but do little to account for subsequent differentiation of ciliated cells and ciliogenesis during normal growth and development.

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