Methylation Profiles of IL33 and CCL26 in Bronchial Epithelial Cells are Associated with Asthma

Abstract

Aim: This study aimed to characterize DNA methylation (DNA-me) in promoter region of IL33, IL1RL1 and CCL26 in asthma and their impacts on transcriptional activity in bronchial epithelial cells (BECs). Patients & methods: We performed bis-pyrosequencing, quantitative real-time PCR and sequencing in BECs from ten asthmatic and ten control individuals. Results: We detected lower DNA-me levels of IL33 and CCL26 in asthmatic than control BECs. No correlation was found between methylation and expression levels. Interestingly, carriers of a mutative allele in a haplotype within the promoter of IL33 had a lower IL33 DNA-me level and CCL26 gene expression correlated with eosinophil count. Conclusion: These findings highlight the importance of investigating both epigenetic and genetic mechanisms in understanding the epithelial immune response in asthma.

Keywords::

• bronchial epithelial cell
• CCL26
• DNA methylation
• eosinophil
• gene expression
• IL33
• IL1RL1

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: https://www.tandfonline.com/doi/suppl/10.2217/epi-2018-0044

Authors’ contributions

M Larouche and V Gagné-Ouellet performed epigenetic and gene expression experimentations, statistical analyses and manuscript redaction under C Laprise direction. AM Boucher-Lafleur participated to epigenetic experimentations. MC Larose and S Plante isolated bronchial epithelial cells and performed cell culture. AM Madore validated the statistical analyses and participated to manuscript redaction. N Flamand and J Chakir participated to the design of the study. M Laviolette performed bronchial biopsies. J Chakir supervised the bronchial epithelial cells isolation and cell culture process. C Laprise designed the complete study and supervised the epigenetic and gene expression experiments, statistical analyses and the redaction of the manuscript. All co-authors approved the final form of the manuscript.

Financial & competing interests disclosure

This work was supported by a catalyst grant awarded to C Laprise from Canadian Institutes of Health Research. C Laprise holds the Canada Research Chair in the Environment and Genetics of Respiratory Disorders and Allergy, directs the Asthma Strategic Group of the Quebec Respiratory Health Network (RHN) of Fonds de recherche du Québec – Santé and is a member of CHILD study and AllerGen NCE. J Chakir, N Flamand, M Laviolette and C Laprise are members of the RHN. M Larouche, V Gagné-Ouellet and AM Boucher-Lafleur received a Summer Student Research Training Award from AllerGen NCE and a master degree studentship award from the RHN. M Larouche and AM Boucher-Lafleur received a master degree studentship award from the Fonds de recherche du Québec – Santé. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical disclosure

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by a catalyst grant awarded to C Laprise from Canadian Institutes of Health Research. C Laprise holds the Canada Research Chair in the Environment and Genetics of Respiratory Disorders and Allergy, directs the Asthma Strategic Group of the Quebec Respiratory Health Network (RHN) of Fonds de recherche du Québec – Santé and is a member of CHILD study and AllerGen NCE. J Chakir, N Flamand, M Laviolette and C Laprise are members of the RHN. M Larouche, V Gagné-Ouellet and AM Boucher-Lafleur received a Summer Student Research Training Award from AllerGen NCE and a master degree studentship award from the RHN. M Larouche and AM Boucher-Lafleur received a master degree studentship award from the Fonds de recherche du Québec – Santé. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.