Reduced IRF7 response to rhinovirus unrelated with DNA methylation in peripheral mononuclear cells of adult asthmatics

Sae-Hoon Kim; Kyung-Hwan Lim; Han-Ki Park; Suh-Young Lee; Soon-Hee Kim; Hye-Ryun Kang; Heung-Woo Park; Yoon-Seok Chang; Sang-Heon Cho

doi:10.5415/apallergy.2015.5.2.114

Reduced IRF7 response to rhinovirus unrelated with DNA methylation in peripheral mononuclear cells of adult asthmatics

Asia Pac Allergy. 2015 Apr;5(2):114-22. doi: 10.5415/apallergy.2015.5.2.114. Epub 2015 Apr 29.

Authors

Sae-Hoon Kim¹, Kyung-Hwan Lim², Han-Ki Park², Suh-Young Lee¹, Soon-Hee Kim³, Hye-Ryun Kang², Heung-Woo Park², Yoon-Seok Chang¹, Sang-Heon Cho²

Affiliations

¹ Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-899, Korea. ; Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul 110-899, Korea. ; Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 463-707, Korea.
² Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-899, Korea. ; Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul 110-899, Korea.
³ Biomedical Research Institute, Seoul National University Bundang Hospital, Seongnam 463-707, Korea.

Abstract

Background: Human rhinoviruses are the major cause of asthma exacerbation in both children and adults. Recently, impaired antiviral interferon (IFN) response in asthmatics has been indicated as a primary reason of the susceptibility to respiratory virus, but the mechanism of defective IFN production is little understood to date. The expression of IFN regulatory factor 7 (IRF7), a transcriptional factor for virus-induced type I IFN production is known to be regulated epigenetically by DNA methylation.

Objective: We aimed to investigate the expression of IFN-α, IFN-β, and IRF7 in response to rhinovirus infection in the adult asthmatics and evaluate DNA methylation status of IRF7 gene promotor.

Methods: Twenty symptomatic adult asthmatics and 10 healthy subjects were enrolled and peripheral blood was collected from each subject. Peripheral blood mononuclear cells (PBMCs) were isolated, cultured, and ex vivo stimulated with rhinovirus-16. The mRNA expressions of IFN-α, IFN-β, and IRF7 were analyzed using real time quantitative polymerase chain reaction. Genomic DNA was isolated from untreated PBMCs and the methylation status of IRF7 gene promotor was investigated using bisulfite pyrosequencing.

Results: The mean age of asthmatics was 45.4 ± 15.7 years and 40% was male, which were not different with those of control group. Asthmatics showed significantly decreased mRNA expressions (relative expression to beta-actin) of IFN-α and IFN-β compared with normal control. The mRNA expression of IRF7 in the asthmatics was also significantly lower than those in the normal control. No significant difference of DNA methylation was observed between asthmatics and controls in all analyzed positions of IRF7 promotor CpG loci.

Conclusion: The mRNA expression of type I IFN in response to rhinovirus was impaired in the PBMCs of adult asthmatics. The mRNA expression of IRF7, transcriptional factor inducing type I IFN was also reduced, but not caused by altered DNA methylation in the IRF7 gene promotor.

Keywords: Asthma; DNA methylation; Interferon type I; Rhinovirus.