Inhibited cell death, NF-kappaB activity and increased IL-10 in TCR-triggered thymocytes of transgenic mice overexpressing the glucocorticoid-induced protein GILZ.
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.
Delfino
Domenico Vittorio
DV
Section of Pharmacology, Department of Clinical and Experimental Medicine, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. midelfin@unipg.it
Agostini
Massimiliano
M
Spinicelli
Stefania
S
Vacca
Carmine
C
Riccardi
Carlo
C
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*
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