Transcriptional regulation of interleukin-2 gene expression by CD69-generated signals

Daniele D'Ambrosio, Rossana Trotta, Alessandra Vacca, Laigi Frati, Angela Santoni, Alberto Gulino, Roberto Testi

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The 5′ flanking region of the human interleukin (IL)-2 gene was investigated for enhancer activity in response to CD69-generated signals, using a chloramphenicol acetyltransferase (CAT)-driven transient expression system in Jurkat cells. The region extending from -317 to +47 relative to the initiation site of IL-2 gene transcription was shown to contain sequences able to respond to CD69 cross-linking, by enhancing by about 100 % a phorbol 12-myristate 13-acetate (PMA)-plus-ionomycin stimulation of CAT activity. A similar increase in CAT activity produced by PMA-plus-anti-CD3 mAb was induced by CD69 cross-linking, while a 200 % increase over that obtained by PMA-plus-anti-CD28 mAb stimulation was seen. Analysis of enhancer deletion mutants revealed that proximal AP-1, OCT-1/octamer-associated protein and nuclear factor of activated T cells (NFAT) binding regions were all necessary to allow CD69-mediated enhancement of CAT activity. By gel mobility shift analysis, cyclosporin A-sensitive NFAT-binding induction and enhancement of AP-1 binding activity could be detected in nuclear extracts of both Jurkat and peripheral blood T cells after simultaneous CD69 and protein kinase C stimulation. Finally, CD69-mediated signals could increase NFAT and AP-1 binding activity following PMA and ionomycin stimulation in peripheral blood T cells. Collectively, these data suggest that CD69-generated signals participate in the control of the IL-2 gene expression at the transcriptional level, likely acting through NFAT and AP-1 transcription factor complexes.

Original languageEnglish
Pages (from-to)2993-2997
Number of pages5
JournalEuropean Journal of Immunology
Volume23
Issue number11
Publication statusPublished - Nov 1993

Fingerprint

NFATC Transcription Factors
Chloramphenicol O-Acetyltransferase
Transcription Factor AP-1
Interleukin-2
Acetates
Gene Expression
Ionomycin
Blood Cells
T-Lymphocytes
Jurkat Cells
5' Flanking Region
Electrophoretic Mobility Shift Assay
Protein Kinase C
Cyclosporine
Genes
phorbol-12-myristate
Proteins

Keywords

  • CD69
  • Interleukin-2

ASJC Scopus subject areas

  • Immunology

Cite this

D'Ambrosio, D., Trotta, R., Vacca, A., Frati, L., Santoni, A., Gulino, A., & Testi, R. (1993). Transcriptional regulation of interleukin-2 gene expression by CD69-generated signals. European Journal of Immunology, 23(11), 2993-2997.

Transcriptional regulation of interleukin-2 gene expression by CD69-generated signals. / D'Ambrosio, Daniele; Trotta, Rossana; Vacca, Alessandra; Frati, Laigi; Santoni, Angela; Gulino, Alberto; Testi, Roberto.

In: European Journal of Immunology, Vol. 23, No. 11, 11.1993, p. 2993-2997.

Research output: Contribution to journalArticle

D'Ambrosio, D, Trotta, R, Vacca, A, Frati, L, Santoni, A, Gulino, A & Testi, R 1993, 'Transcriptional regulation of interleukin-2 gene expression by CD69-generated signals', European Journal of Immunology, vol. 23, no. 11, pp. 2993-2997.
D'Ambrosio D, Trotta R, Vacca A, Frati L, Santoni A, Gulino A et al. Transcriptional regulation of interleukin-2 gene expression by CD69-generated signals. European Journal of Immunology. 1993 Nov;23(11):2993-2997.
D'Ambrosio, Daniele ; Trotta, Rossana ; Vacca, Alessandra ; Frati, Laigi ; Santoni, Angela ; Gulino, Alberto ; Testi, Roberto. / Transcriptional regulation of interleukin-2 gene expression by CD69-generated signals. In: European Journal of Immunology. 1993 ; Vol. 23, No. 11. pp. 2993-2997.
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