Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.1004604 on October 4, 2005

Published online before print October 4, 2005
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(Journal of Leukocyte Biology. 2005;78:1339-1346.)
© 2005 by Society for Leukocyte Biology

Different signaling pathways inhibit DNA methylation activity and up-regulate IFN-{gamma} in human lymphocytes

Victoria Bonilla-Henao, Raquel Martínez, Francisco Sobrino and Elizabeth Pintado1

Departamento de Bioquímica Médica y Biología Molecular, Facultad de Medicina y Hospital Universitario Virgen Macarena, Universidad de Sevilla, Spain

1 Correspondence: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Avda. Sanchez Pizjuán, 4, E-41009, Sevilla, Spain. E-mail: elizabet{at}us.es

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.

Key Words: DNA methyltransferases • PKC • phosphatase inhibitors • sulfhydryl-blocking reagents






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