c-Rel regulation of IL-2 gene expression may be mediated through activation of AP-1

Virginia Smith Shapiro, Marianne Newton Mollenauer, Warner C. Greene, Arthur Weiss

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

T cell activation by antigen/MHC induces the expression of several genes critical to the immune response, including interleukin-2. T cells from mice deficient for the NF-κB family member c-rel cannot activate IL-2 gene expression. However, mutating the NF-κB site in the IL-2 promoter has only moderate effects. To investigate additional ways c-Rel could regulate IL-2 gene expression, we determined whether c-rel overexpression could increase the activity of other transcription factors involved in IL-2 promoter regulation: NF-AT, Oct/OAP (ARRE-1), and AP-1. In jurkat TAg cells, overexpression of c-Rel increased AP-1 activation ~17-fold. Moreover, AP-1 activity stimulated by anti-TCR Abs or PMA/ionomycin was further increased by c-Rel overexpression. c-Rel overexpression did not affect NF-AT or ARRE-1 activity. Additionally, overexpression of c-Rel activated the nonconsensus AP-1 site from the IL-2 promoter (NF-IL-2B), although to a lesser extent, approximately sixfold. AP-1 activation required both the DNA binding and transactivation domains of c-Rel. Our results may provide an explanation for the effect on IL-2 gene activation in c-rel-deficient mice.

Original languageEnglish (US)
Pages (from-to)1663-1669
Number of pages7
JournalJournal of Experimental Medicine
Volume184
Issue number5
DOIs
StatePublished - Nov 1 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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