Mechanisms in interleukin-2 protection against glucocorticoid-induced apoptosis: regulation of AP-1 and glucocorticoid receptor transcriptional activities

J Interferon Cytokine Res. 1996 Aug;16(8):601-9. doi: 10.1089/jir.1996.16.601.


We have used the gibbon ape leukemia cell line MLA-144 and its corticoid-sensitive subclone MLA-E7T to analyze the mechanisms whereby interleukin-2 (IL-2) can protect T cells against dexamethasone-induced apoptosis. MLA cells are characterized by the constitutive expression of intermediate affinity receptors for IL-2, together with IL-4 receptors. MLA-144 cells secrete IL-2 and are insensitive to dexamethasone, whereas MLA-E7T cells do not constitutively produce significant amounts of IL-2 and undergo apoptotic cell death in the presence of dexamethasone. Exogenous IL-2 was shown to protect MLA-E7T cells against the apoptotic effect of dexamethasone and to increase both the DNA binding and transactivating functions of activator protein-1 (AP-1). The functional relationship between AP-1 and glucocorticoid receptors transcriptional activities was further investigated using transient expression of reporter gene constructs whose transcriptions are regulated by promoters containing TPA-responsive elements or glucocorticoid-responsive elements. The data reported here demonstrate that in MLA-144 cells, IL-2 or PMA stimulation antagonizes the glucocorticoid receptor, whereas in MLA-E7T, synergistic effects are observed between dexamethasone and IL-2 or PMA for transactivation of MMTV-CAT. Taken together with the finding that IL-2 but not PMA protects MLA-E7T from dexamethasone-induced apoptosis, our results indicate that IL-2 does not induce such a protection by repressing the transcriptional activity of the glucocorticoid receptor.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / drug effects
  • Antigens, CD / metabolism
  • Apoptosis / drug effects*
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Dexamethasone / antagonists & inhibitors*
  • Dexamethasone / pharmacology
  • Gene Expression Regulation, Leukemic / drug effects*
  • Genes, Reporter
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / metabolism
  • Interleukin-2 / pharmacology*
  • Leukemia Virus, Gibbon Ape
  • Leukemia, T-Cell / pathology
  • Receptors, Glucocorticoid / physiology*
  • Receptors, Interleukin / drug effects
  • Receptors, Interleukin / metabolism
  • Receptors, Interleukin-2 / drug effects
  • Receptors, Interleukin-2 / metabolism
  • Receptors, Interleukin-4
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription Factor AP-1 / physiology*
  • Transcriptional Activation / drug effects
  • Tumor Cells, Cultured / drug effects


  • Antigens, CD
  • Interleukin-2
  • Receptors, Glucocorticoid
  • Receptors, Interleukin
  • Receptors, Interleukin-2
  • Receptors, Interleukin-4
  • Recombinant Fusion Proteins
  • Transcription Factor AP-1
  • Dexamethasone
  • Tetradecanoylphorbol Acetate