Transcriptional regulation of the interleukin 2 gene by glucocorticoid hormones. Role of steroid receptor and antigen-responsive 5'-flanking sequences

A. Vacca, S. Martinotti, I. Screpanti, M. Maroder, M. P. Felli, A. R. Farina, A. Gismondi, A. Santoni, L. Frati, A. Gulino

Research output: Contribution to journalArticle

Abstract

Dexamethasone treatment of the Jurkat T77 cell clone inhibited the enhancing effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) and the calcium ionophore A23187 on the interleukin 2 (IL2) mRNA levels and gene transcription from intact nuclei. Dexamethasone treatment of Jurkat T77 cells inhibited the TPA/A23187-dependent activation of the transcription from the transfected pIL2CAT, containing 600 base pairs of the genomic sequences upstream of the coding region of IL2 gene, including the TPA/calcium responsive cis-regulatory elements and promoter sequences, driving the expression of the chloramphenicol acetyltransferase (CAT) gene. Transfection of either Jurkat T77 cell clone or glucocorticoid-resistant Jurkat cells with a human glucocorticoid receptor cDNA under the transcriptional control of the Rous sarcoma virus long terminal repeat (LTR) (pRShGRα) significantly increased or induced, respectively, the dexamethasone-mediated inhibition of the TPA/A23187-dependent expression of pIL2-CAT as well as the enhancing effect on the expression of the cotransfected CAT gene under the control of the mouse mammary tumor virus LTR, as a marker of glucocorticoid receptor action. This suggests a role for the glucocorticoid receptor in mediating the dexamethasone action on IL2 gene expression. To study the cis-regulatory sequence specificity of the dexamethasone-induced interference with the TPA/A23187-mediated T cell activating signals, we studied the effect of the hormone on the regulatory elements contained in the Rous sarcoma virus and human T lymphotropic virus 1 long terminal repeats and the SV40 promoter, which are known to be transcriptionally enhanced by those activating agents. Dexamethasone was unable to interfere with the TPA/A23187-mediated enhancement of these cis-regulatory elements, suggesting that the hormone effect is specific for IL-2 gene sequences. Our data suggest that the dexamethasone-mediated transcriptional inhibition of the IL2 gene is mediated by an interference with the protein kinase C and calcium-mediated trans-activation of the antigen-responsive and T cell-specific elements lying in the 5'-flanking region of the gene.

Original languageEnglish
Pages (from-to)8075-8080
Number of pages6
JournalJournal of Biological Chemistry
Volume265
Issue number14
Publication statusPublished - 1990

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry

Cite this

Vacca, A., Martinotti, S., Screpanti, I., Maroder, M., Felli, M. P., Farina, A. R., Gismondi, A., Santoni, A., Frati, L., & Gulino, A. (1990). Transcriptional regulation of the interleukin 2 gene by glucocorticoid hormones. Role of steroid receptor and antigen-responsive 5'-flanking sequences. Journal of Biological Chemistry, 265(14), 8075-8080.