Dexamethasone inhibits human interleukin 2 but not interleukin 2 receptor gene expression in vitro at the level of nuclear transcription

• Published in: The Journal of clinical investigation 1991-05, Vol.87 (5), p.1739-1747
• Main Authors: BOUMPAS, D. T, ANASTASSIOU, E. D, OLDER, S. A, TSOKOS, G. C, NELSON, D. L, BALOW, J. E
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Dexamethasone - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Humans; Interleukin-2 - biosynthesis; Interleukin-2 - genetics; Molecular and cellular biology; Molecular genetics; Receptors, Interleukin-2 - genetics; RNA, Messenger - metabolism; Transcription, Genetic - drug effects
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI115192

Glucocorticosteroids have an inhibitory effect on the expression of interleukin 2 (IL-2) and interleukin 2 receptor (IL-2R) genes. To determine the mechanisms of this inhibition, human T lymphocytes were stimulated with mitogens in the presence of dexamethasone. Nuclear transcription run-off assays showed that high doses of dexamethasone inhibited the transcription of the IL-2 gene but not that of the IL-2R gene. Post-transcriptionally, high doses of dexamethasone (10(-4) M) were required to inhibit IL-2R mRNA levels by 50%, whereas lower doses (10(-6) M) inhibited by greater than 70% the accumulation of IL-2 mRNA. IL-2 mRNA half-life decreased in the presence of dexamethasone (10(-6) M) by approximately 50%. At the protein product level, dexamethasone inhibited both IL-2 production, as well as cell surface and soluble forms of IL-2R. IL-2R gene expression was inhibited for at least 72 h after exposure of cells to dexamethasone. In the presence of exogenous IL-2, dexamethasone failed to exert a significant effect on the production of IL-2R protein. These data indicate that dexamethasone has a greater effect on the expression of the IL-2 gene than on the IL-2R gene. Dexamethasone both inhibits transcription of the IL-2 gene and decreases the stability of IL-2 mRNA. The effect of dexamethasone on the IL-2R gene is post-transcriptional and may result indirectly from decreased IL-2 production.