BINDING OF NUCLEAR PROTEINS TO THE NEGATIVE REGULATORY ELEMENT OF THE IL-2 GENE IN LYMPHOCYTES FROM RHEUMATIC PATIENTS

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 1999-03, Vol.11 (3), p.187-191
• Main Authors: Flescher, E., Vela-Roch, N., Talal, N., Dang, H.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - metabolism; Binding Sites - genetics; Case-Control Studies; DNA-Binding Proteins - metabolism; Female; Humans; IL-2/NRE-A/rheumatoid arthritis/systemic lupus erythematosus/transcription factors; In Vitro Techniques; Interleukin-2 - biosynthesis; Interleukin-2 - genetics; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - metabolism; Lymphocyte Activation; Male; Middle Aged; Nuclear Proteins - metabolism; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1006/cyto.1998.0425

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.