Hydralazine and procainamide inhibit T cell DNA methylation and induce autoreactivity

Inhibitors of DNA methylation, such as 5-azacytidine, induce gene expression. We have previously reported that cloned T cells treated with 5-azacytidine lose the requirement for Ag and can be activated by autologous HLA-D molecules alone, thus becoming auto-reactive. This phenomenon could potentiall...

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Bibliographic Details
Published inThe Journal of immunology (1950) Vol. 140; no. 7; pp. 2197 - 2200
Main Authors Cornacchia, E, Golbus, J, Maybaum, J, Strahler, J, Hanash, S, Richardson, B
Format Journal Article
LanguageEnglish
Published Bethesda, MD Am Assoc Immnol 01.04.1988
American Association of Immunologists
Subjects
Antiarythmic agents
Autoimmune Diseases - chemically induced
Autoimmune Diseases - enzymology
Autoimmune Diseases - immunology
Biological and medical sciences
Cardiovascular system
DNA (Cytosine-5-)-Methyltransferases - antagonists & inhibitors
Humans
Hydralazine - adverse effects
Hydralazine - pharmacology
Immunosuppressive Agents - adverse effects
Immunosuppressive Agents - pharmacology
Lupus Vulgaris - chemically induced
Lupus Vulgaris - immunology
Lymphocyte Activation - drug effects
Medical sciences
Pharmacology. Drug treatments
Procainamide - adverse effects
Procainamide - pharmacology
T-Lymphocytes - drug effects
T-Lymphocytes - enzymology
T-Lymphocytes - immunology
Inhibition
Methylation
DNA
Antiarrhythmia agent
T-Lymphocyte
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Summary:Inhibitors of DNA methylation, such as 5-azacytidine, induce gene expression. We have previously reported that cloned T cells treated with 5-azacytidine lose the requirement for Ag and can be activated by autologous HLA-D molecules alone, thus becoming auto-reactive. This phenomenon could potentially mediate an autoimmune disease in vivo. Inasmuch as several drugs are known to cause autoimmune disease, we asked whether they exert the same effects on T cells as 5-azacytidine. We report that hydralazine and procainamide, two drugs associated with a lupus-like autoimmune disease, also inhibit DNA methylation and induce self-reactivity in cloned T cell lines. These results suggest that drug-induced autoimmune disease may be due to activation of as yet unidentified genes through mechanisms involving DNA methylation.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.140.7.2197