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


CONCLUSIONS
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.
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.
Sae-Hoon
SH
Kim
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.
Kyung-Hwan
KH
Lim
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.
Han-Ki
HK
Park
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.
Suh-Young
SY
Lee
Biomedical Research Institute, Seoul National University Bundang Hospital, Seongnam 463-707, Korea.
Soon-Hee
SH
Kim
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.
Hye-Ryun
HR
Kang
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.
Heung-Woo
HW
Park
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.
Yoon-Seok
YS
Chang
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.
Sang-Heon
SH
Cho
Asthma; DNA methylation; Interferon type I; Rhinovirus