MECHANISMS IN INTERLEUKIN-2 PROTECTION AGAINST GLUCOCORTICOID-INDUCEDAPOPTOSIS - REGULATION OF AP-1 AND GLUCOCORTICOID RECEPTOR TRANSCRIPTIONAL ACTIVITIES

We have used the gibbon ape leukemia cell line MLA-144 and its cortico id-sensitive subclone MLA-E7T to analyze the mechanisms whereby interl eukin-2 (IL-2) can protect T cells against dexamethasone-induced apopt osis, MLA cells are characterized by the constitutive expression of in termediate affinity receptors for IL-2, together with IL-4 receptors, MLA-144 cells secrete IL-2 and are insensitive to dexamethasone, where as 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 apopto tic effect of dexamethasone and to increase both the DNA binding and t ransactivating functions of activator protein-1 (AP-1), The functional relationship between AP-1 and glucocorticoid receptors transcriptiona l activities was further investigated using transient expression of re porter gene constructs whose transcriptions are regulated by promoters containing TPA-responsive elements or glucocorticoid-responsive eleme nts. The data reported here demonstrate that in MLA-144 cells, IL-2 or PMA stimulation antagonizes the glucocorticoid receptor, whereas in M LA-E7T, synergistic effects are observed between dexamethasone and IL- 2 or PMA for transactivation of MMTV-CAT, Taken together with the find ing that IL-2 but not PMA protects MLA-E7T from dexamethasone-induced apoptosis, our results indicate that IL-2 does not induce such a prote ction by repressing the transcriptional activity of the glucocorticoid receptor.