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

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

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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.