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DNA methylation and the expression of IL-4 and IFN-gamma promoter genes in patients with bronchial asthma.

Abstract：

:Although CpG methylation is thought to be a negative regulator of gene transcription, its relationship with cytokine expression remains unclear. Interleukin (IL)-4 and interferon (IFN)-gamma are major cytokines that affect the differentiation of naïve CD4+ T lymphocytes into the Th1 and Th2 lineage. We used bisulfite deoxyribonucleic acid modification and sequencing to examine the relationship between CpG methylation and IL-4 and IFN-gamma gene expression before and after allergen stimulation in human CD4+ T lymphocytes from sensitized hosts. In naïve cells, the CpGs in the promoter regions were methylated largely in both the IL-4 and IFN-gamma genes. After Dermatophagoides pteronyssinus/Dermatophagoides farinae stimulation, the degree of unmethylation in the IL-4 gene increased in cells from patients with bronchial asthma. After phytohemagglutinin stimulation, the degree of unmethylation increased in cells from nonallergic control subjects. The concentration of IL-4 was strongly correlated with the degree of unmethylation in the patient group. These data suggest that CpGs located at -80 of the IL-4 gene and at -295, -186, and +122 of the IFN-gamma gene have regulatory activities important for cytokine expression. We conclude that the stimulation of CD4+ T lymphocytes causes considerable increases in the degree of unmethylation and that in sensitized hosts, the extent of unmethylation correlates with the concentration of IL-4.

journal_name

J Clin Immunol

journal_title

Journal of clinical immunology

authors

Kwon NH,Kim JS,Lee JY,Oh MJ,Choi DC

doi

10.1007/s10875-007-9148-1

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

139-46

issue

2

eissn

0271-9142

issn

1573-2592

journal_volume

28

pub_type

杂志文章

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