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 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.
Cornacchia
E
E
Department of Internal Medicine, University of Michigan, Ann Arbor 48109.
Golbus
J
J
Maybaum
J
J
Strahler
J
J
Hanash
S
S
Richardson
B
B
D001327:Autoimmune Diseases / Q000139:chemically induced / Q000201:enzymology* / Q000276:immunology; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors*; D006801:Humans; D006830:Hydralazine / Q000009:adverse effects / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology; D008177:Lupus Vulgaris / Q000139:chemically induced / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D011342:Procainamide / Q000009:adverse effects / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology
D007166:Immunosuppressive Agents; D006830:Hydralazine; D004248:DNA (Cytosine-5-)-Methyltransferases; D011342:Procainamide