Cyclosporin A sensitivity of the NF-κB site of the IL2Rα promoter in untransformed murine T cells

Patricia G. McCaffrey, Peter K. Kim, Viia E. Valge-Archer, Ranjan Sen, Anjana Rao

Research output: Contribution to journalArticlepeer-review

Abstract

We have investigated the characteristics of IL2Rα gene induction in untransformed murine T cells. Induction of IL2Rα mRNA by TCR/CD3 ligands in a murine T cell clone and in short-term splenic T cell cultures was inhibited by protein synthesis inhibitors and by CsA. This result was contrary to previous observations in JURKAT T leukemia cells and human peripheral blood T cells, suggesting a difference in the mechanisms of IL2Rα gene induction in these different cell types. The CsA sensitivity of IL2Rα mRNA induction represented a direct effect on the TCR/CD3 response, and was not due to CsA-sensitive release of the lymphokines IL2 or tumour necrosis factor α (TNFα) and consequent lymphokine-mediated induction of IL2Rα mRNA. The NF-κB site of the IL2Rα promoter was essential for gene induction through the TCR/CD3 complex, and the induction of reporter plasmids containing multimers of this site was significantly inhibited by CsA. Northern blotting analysis indicated that while the p65 subunit of NF-κB was constitutively expressed and not appreciably induced upon T cell activation, mRNA for the p105 precursor of p50 NF-κB was induced in response to TCR/CD3 stimulation and this induction was sensitive to CsA. Electrophoretic mobility shift assays and antiserum against the p50 subunit of NF-κB indicated that p50 was a component of the inducible nuclear complex that bound to the IL2Rα κB site. Appearance of the kB-binding proteins was insensitive to CsA at early times after activation (~15 min), but was partially sensitive to CsA at later times. Based on these results, we propose that the NF-κB site of the IL2Rα promoter mediates at least part of the CsA sensitivity of IL2Rα gene induction in untransformed T cells, possibly because de novo synthesis of p105 NF-κB is required for sustained IL2Rα expression.

Original languageEnglish (US)
Pages (from-to)2134-2142
Number of pages9
JournalNucleic Acids Research
Volume22
Issue number11
StatePublished - Jun 11 1994
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Health, Toxicology and Mutagenesis
  • Toxicology
  • Genetics(clinical)

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