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

Krawczyk, Krzysztof; Acharya, Shinjita; Tan, Ge; Wawrzyniak, Marcin; Karouzakis, Emmanuel; Dreher, Anita; Jakieła, Bogdan; Altunbulakli, Can; Sanak, Marek; O’Mahony, Liam; Nadeau, Kari; Akdiş, Cezmi A.

doi:10.1111/all.14667

Cited by 13 publications

(20 citation statements)

References 9 publications

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“…The inversion of CpG methylation diminishes epithelium leakiness and increases the expression of tight junctions' proteins. 61 Moreover, the methylation status of inflammatory genes differentiates asthma patients from non-asthmatic subjects. 62 Decreased methylation and low expression of vanin-1 gene are associated with poor response to inhaled corticosteroids (ICS), whereas increased availability of cysteamine, a product of vanin-1 pathway, protects from AHR.…”

Section: Shared Mechanismsmentioning

confidence: 99%

Advances and highlights in asthma in 2021

Agache

Eguiluz‐Gracia

Cojanu

et al. 2021

Allergy

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Last year brought a significant advance in asthma management, unyielding to the pressure of the pandemics. Novel key findings in asthma pathogenesis focus on the resident cell compartment, epigenetics and the innate immune system. The precision immunology unbiased approach was supplemented with novel tools and greatly facilitated by the use of artificial intelligence. Several randomised clinical trials and good quality realworld evidence shed new light on asthma treatment and supported the revision of several asthma guidelines (GINA, Expert Panel Report 3, ERS/ATS guidelines on severe asthma) and the conception of new ones (EAACI Guidelines for the use of biologicals in severe asthma). Integrating asthma management within the broader context of Planetary Health has been put forward. In this review, recently published articles and clinical trials are summarised and discussed with the goal to provide clinicians and researchers with a concise update on asthma research from a translational perspective.

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Section: Shared Mechanismsmentioning

confidence: 99%

Advances and highlights in asthma in 2021

Agache

Eguiluz‐Gracia

Cojanu

et al. 2021

Allergy

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“…Another pioneer study of DNA methylation in nasal cells from asthmatics ( n = 35, Caucasian children population) showed that FeNO (fractional exhaled nitric oxide) is negatively associated with IL6 and iNOs methylation. While global methylation has been found higher in BECs of asthmatics, 30 Alu and LINE1‐global methylation was not linked to FeNO and FEV1 (Forced Expiratory Volume) in nasal epithelial cells (NECs). Decreased methylation of IL6 promoter was associated with higher FENO as shown in multivariable regression in an independent fashion of the iNOS promoter status.…”

Section: Dna Methylation In Nasal Epithelial Cells (Necs)mentioning

confidence: 97%

“…Another study did not directly measure methylation changes, but targeted epigenetic modifying enzymes instead and assessed expression of 82 genes across 5 families(30), with linear regression showing reduced mRNA expression of the kinase Aurora Kinase A (AURKA), the ligase DZIP3, the methyltransferases Euchromatic Histone Lysine Methyltransferase 2 (EHMT2) and Suppressor Of Variegation three to nine Homolog 1 (SUV39H1), as well as increased mRNA expression of the acetyltransferases CREB Binding Protein (CREBBP) and E1A Binding Protein P300 (EP300). Notably, regarding genes involved in epigenetic processes, Tet Methylcytosine Dioxygenase 1 (TET1), which is involved in DNA demethylation, was found to be methylated in another study which used in air‐liquid interface cultures of asthmatic BECs, 30 whereas Protein Arginine Methyltransferase 1 (PRMT1), a histone methyltransferase, was not. The same study also found higher global methylation levels in asthmatic BECs, and their list of the top 100 group of highly methylated genes includes the previously mentioned LCN6, CCL26, CREBBP and TNXB, with several of the rest of the genes associated with cytoskeletal remodeling, cell growth, ion transport, metabolism, T‐cell signaling pathway, and bronchial barrier regulation (Table 1 ).…”

Section: Differential Dna Methylation In Bronchial Epithelial Cellsmentioning

confidence: 99%

“…When we compared the three EWAS in NECs (EVA‐PR study, Inner City Consortium and Project VIVA; Table S2 ), after considering only the methylation status of allergic/atopic asthma and including all the presented genes with statistical significance, two shared gene loci are identified: PCSK6 and TSHR. PSCK6 has also been differentially expressed in bronchial brushings between cigarette smoking severe asthma and nonsmoking severe asthma 111 and has been mentioned to be induced in vitro by interleukin (IL)‐4 and IL‐13, to activate NF‐κB, IL‐1, and IL‐6, 25 to have a paracrine role in activating matrix metalloproteases 30 and participate in glycoprotein metabolic process and endopeptidase inhibitor activity. Giovannini‐Chami et al.…”

Section: Dna Methylation Comparisons Among Studies and Across Tissuesmentioning

confidence: 99%

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DNA methylation biomarkers in asthma and rhinitis: Are we there yet?

Legaki

Arsenis

Τaka

et al. 2022

Clinical & Translational All

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The study of epigenetics has improved our understanding of mechanisms underpinning gene‐environment interactions and is providing new insights in the pathophysiology of respiratory allergic diseases. We reviewed the literature on DNA methylation patterns across different tissues in asthma and/or rhinitis and attempted to elucidate differentially methylated loci that could be used to characterize asthma or rhinitis. Although nasal and bronchial epithelia are similar in their histological structure and cellular composition, genetic and epigenetic regulation may differ across tissues. Advanced methods have enabled comprehensive, high‐throughput methylation profiling of different tissues (bronchial or nasal epithelial cells, whole blood or isolated mononuclear cells), in subjects with respiratory conditions, aiming to elucidate gene regulation mechanisms and identify new biomarkers. Several genes and CpGs have been suggested as asthma biomarkers, though research on allergic rhinitis is still lacking. The most common differentially methylated loci presented in both blood and nasal samples are ACOT7, EPX, KCNH2, SIGLEC8, TNIK, FOXP1, ATPAF2, ZNF862, ADORA3, ARID3A, IL5RA, METRNL and ZFPM1. Overall, there is substantial variation among studies, (i.e. sample sizes, age groups and disease phenotype). Greater variability of analysis method detailed phenotypic characterization and age stratification should be taken into account in future studies.

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“…[ 138 ] Inhibition of CpG methylation was found to improve the integrity of the bronchial epithelial barrier in asthma. [ 139 ] Parkinson's disease-associated gene could also protect against HDM-induced airway epithelial barrier impairment by attenuating epithelial cell pyroptosis. [ 127 ] Nitric oxide promoted airway epithelial wound repair through increasing the activity of matrix metalloproteinases 9.…”

Section: Restoration Of the Airway Epithelial Barriermentioning

confidence: 99%

Involvement and therapeutic implications of airway epithelial barrier dysfunction in type 2 inflammation of asthma

Ding

Zhang

Öğülür

et al. 2022

Chinese Medical Journal

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Type 2 inflammation is a complex immune response and primary mechanism for several common allergic diseases including allergic rhinitis, allergic asthma, atopic dermatitis, and chronic rhinosinusitis with nasal polyps. It is the predominant type of immune response against helminths to prevent their tissue infiltration and induce their expulsion. Recent studies suggest that epithelial barrier dysfunction contributes to the development of type 2 inflammation in asthma, which may partly explain the increasing prevalence of asthma in China and around the globe. The epithelial barrier hypothesis has recently been proposed and has received great interest from the scientific community. The development of leaky epithelial barriers leads to microbial dysbiosis and the translocation of bacteria to inter- and sub-epithelial areas and the development of epithelial tissue inflammation. Accordingly, preventing the impairment and promoting the restoration of a deteriorated airway epithelial barrier represents a promising strategy for the treatment of asthma. This review introduces the interaction between type 2 inflammation and the airway epithelial barrier in asthma, the structure and molecular composition of the airway epithelial barrier, and the assessment of epithelial barrier integrity. The role of airway epithelial barrier disruption in the pathogenesis of asthma will be discussed. In addition, the possible mechanisms underlying the airway epithelial barrier dysfunction induced by allergens and environmental pollutants, and current treatments to restore the airway epithelial barrier are reviewed.

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

Abstract: 6. Atherton HC, Jones G, Danahay H. IL-13-induced changes in the goblet cell density of human bronchial epithelial cell cultures: MAP kinase and phosphatidylinositol 3-kinase regulation.

Cited by 13 publications

References 9 publications

Advances and highlights in asthma in 2021

Advances and highlights in asthma in 2021

DNA methylation biomarkers in asthma and rhinitis: Are we there yet?

Involvement and therapeutic implications of airway epithelial barrier dysfunction in type 2 inflammation of asthma

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