title: Inhibited cell death, NF-kappaB activity and increased IL-10 in TCR-triggered thymocytes of transgenic mice overexpressing the glucocorticoid-induced protein GILZ.
abstract: Glucocorticoids promote thymocyte apoptosis and modulate transcription of several genes including GILZ, which is strongly up-regulated in the thymus. We used transgenic mice overexpressing GILZ in the T-cell lineage to investigate TCR-triggered functions of GILZ-overexpressing thymocytes. TCR-triggered apoptosis, but not glucocorticoid-induced apoptosis, was inhibited in transgenic mice compared to their controls. In vivo anti-CD3 administration did not reduce CD4(+)CD8(+) thymocyte number. Analysis of TCR-triggered molecular changes indicated that p65 NF-kappaB nuclear translocation and DNA binding activity was inhibited in transgenic mice, which might be linked with apoptosis inhibition. IL-10 release increased whereas release of IL-2, IFN-gamma, IL-13 and IL-4 remained unchanged. These results support the hypothesis that GILZ regulates, at least in part, T-cell development by influencing thymus function at cellular and molecular levels.
authors.affiliation: Section of Pharmacology, Department of Clinical and Experimental Medicine, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. midelfin@unipg.it
authors.forename: Domenico Vittorio
authors.initials: DV
authors.lastname: Delfino
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Agostini
authors.forename: Stefania
authors.initials: S
authors.lastname: Spinicelli
authors.forename: Carmine
authors.initials: C
authors.lastname: Vacca
authors.forename: Carlo
authors.initials: C
authors.lastname: Riccardi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D017209:Apoptosis; D017252:CD3 Complex / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis*; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016207:Cytokines; C498608:Dsip1 protein, mouse; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D016753:Interleukin-10