Different signaling pathways inhibit DNA methylation activity and up-regulate IFN-gamma 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 activity in a dose-dependent manner. This inhibition correlates with the induction of the interferon-gamma (IFN-gamma) 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-gamma gene expression, thus suggesting a link between both effects.
Bonilla-Henao
Victoria
V
Departamento de Bioquímica Médica y Biología Molecular, Facultad de Medicina y Hospital Universitario Virgen Macarena, Universidad de Sevilla, Spain.
Martínez
Raquel
R
Sobrino
Francisco
F
Pintado
Elizabeth
E
D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004790:Enzyme Induction / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019169:Jurkat Cells; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D007371:Interferon-gamma; D004247:DNA; D004248:DNA (Cytosine-5-)-Methyltransferases; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases