Binding of nuclear proteins to the negative regulatory element of the IL-2 gene in lymphocytes from rheumatic patients.
T lymphocytes from several autoimmune diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) exhibit deficient mitogenic response in terms of proliferation and IL-2 production. The expression of the IL-2 gene is regulated by various transcription factors. One of these factors suppresses IL-2 expression and binds to the negative responsive element in the IL-2 gene 5' flanking region (NRE-A). The authors hypothesized that the decreased production of IL-2 by T cells from RA and SLE patients is at least partially caused by high expression of the NRE-A binding protein. To test this hypothesis T cells from healthy donors and patients with RA and SLE were stimulated. Using the electrophoretic mobility shift assay we detected NRE-A DNA-binding proteins in the nuclei of the stimulated cells. No difference was found between NRE-A DNA binding in nuclear extracts of T cells taken from healthy donors and those taken from patients. The specificity of the DNA-protein interactions was ascertained through the use of unlabeled DNA competitors. No correlation was found between DNA-binding and the patients' disease duration or medication. In conclusion, decreased IL-2 biosynthesis by T lymphocytes from RA and SLE patients can not be explained by abnormal expression of the NRE-A DNA-binding protein.
Flescher
E
E
Department of Human Microbiology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. flascher@post.tau.ac.il
Vela-Roch
N
N
Talal
N
N
Dang
H
H
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D009687:Nuclear Proteins