title: Mechanisms in interleukin-2 protection against glucocorticoid-induced apoptosis: regulation of AP-1 and glucocorticoid receptor transcriptional activities.
abstract: 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.
authors.affiliation: CJF INSERM 93-01, Faculté de Pharmacie-Paris XI, Châtenay Malabry, France.
authors.forename: L
authors.initials: L
authors.lastname: Guizani
authors.forename: M
authors.initials: M
authors.lastname: Perrin-Wolff
authors.forename: J
authors.initials: J
authors.lastname: Breard
authors.forename: B
authors.initials: B
authors.lastname: Binetruy
authors.forename: J
authors.initials: J
authors.lastname: Bertoglio
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000187:drug effects / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003907:Dexamethasone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D017930:Genes, Reporter; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D017989:Leukemia Virus, Gibbon Ape; D015458:Leukemia, T-Cell / Q000473:pathology; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D018123:Receptors, Interleukin / Q000187:drug effects / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000378:metabolism; D019948:Receptors, Interleukin-4; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000502:physiology*; D015533:Transcriptional Activation / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D015703:Antigens, CD; D007376:Interleukin-2; D011965:Receptors, Glucocorticoid; D018123:Receptors, Interleukin; D015375:Receptors, Interleukin-2; D019948:Receptors, Interleukin-4; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D003907:Dexamethasone; D013755:Tetradecanoylphorbol Acetate