Different signaling pathways inhibit DNA methylation activity and up-regulate IFN-γ in human lymphocytes

DNA methylation is recognized increasingly for its prominent role in controlling diverse immune processes. In this study, we show that in Jurkat T cells and fresh peripheral lymphocytes, short‐time incubation with protein kinase C activators or phosphatase inhibitors down‐regulate DNA methylation ac...

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Bibliographic Details
Published in:Journal of leukocyte biology 2005-12, Vol.78 (6), p.1339-1346
Main Authors: Bonilla‐Henao, Victoria, Martínez, Raquel, Sobrino, Francisco, Pintado, Elizabeth
Format: Article
Language:English
Subjects:
Cells, Cultured
DNA (Cytosine-5-)-Methyltransferases - genetics
DNA (Cytosine-5-)-Methyltransferases - metabolism
DNA - drug effects
DNA - metabolism
DNA Methylation - drug effects
DNA methyltransferases
Dose-Response Relationship, Drug
Down-Regulation - drug effects
Down-Regulation - genetics
Down-Regulation - immunology
Enzyme Activation - drug effects
Enzyme Activation - physiology
Enzyme Induction - genetics
Enzyme Inhibitors - pharmacology
Gene Expression Regulation - drug effects
Gene Expression Regulation - genetics
Gene Expression Regulation - immunology
Humans
Immunity, Cellular - drug effects
Immunity, Cellular - genetics
Immunity, Cellular - immunology
Interferon-gamma - genetics
Interferon-gamma - immunology
Interferon-gamma - metabolism
Jurkat Cells
Lymphocytes - immunology
Lymphocytes - metabolism
phosphatase inhibitors
Phosphoprotein Phosphatases - antagonists & inhibitors
Phosphoprotein Phosphatases - metabolism
PKC
Promoter Regions, Genetic - genetics
Protein Kinase C - drug effects
Protein Kinase C - metabolism
RNA, Messenger - metabolism
Signal Transduction - genetics
Signal Transduction - immunology
sulfhydryl‐blocking reagents
Up-Regulation - genetics
Up-Regulation - immunology
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Summary:DNA methylation is recognized increasingly for its prominent role in controlling diverse immune processes. In this study, we show that in Jurkat T cells and fresh peripheral lymphocytes, short‐time incubation with protein kinase C activators or phosphatase inhibitors down‐regulate DNA methylation activity in a dose‐dependent manner. This inhibition correlates with the induction of the interferon‐γ (IFN‐γ) gene, which contains several CG sequences in its promoter. The expression of mRNA and protein of the different DNA methyltransferases did not decrease after the treatment. In addition, sulfydryl reagents have a strong inhibitory effect on DNA methylation activity and also induce IFN‐γ gene expression, thus suggesting a link between both effects.
ISSN:0741-5400
1938-3673
DOI:10.1189/jlb.1004604