Glucocorticoid hormone-induced modulation of gene expression and regulation of T-cell death: role of GITR and GILZ, two dexamethasone-induced genes.
Regulation of T-cell survival is a physiological process involved in determining the immune response development, and also the expansion of T-cell tumours. Glucocorticoid hormones (GCH) have been implicated as regulators of T-lymphocyte growth and differentiation. In particular, GCH which by themselves are apoptosis activators and induce T-cell death, can also counteract apoptosis activated by other stimuli, for example antigen-TCR interaction. A number of biochemical events constitute different GCH-activated death-triggering pathways and transcription activity regulation, either upstream and/or downstream in the pathways, is essential to apoptosis. Similarly, GCH-mediated inhibition of apoptosis also requires gene transcription regulation. In particular, between a number of GCH-induced genes, GITR and GILZ can inhibit apoptosis through interaction with mechanisms involved in T-cell survival regulation including the NF-kappaB transcription activity and the expression of the Fas/FasL system. These observations indicate that this GCH-activated dual effect, induction and/or inhibition of T-cell death, requires transcription regulation.
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Department of Clinical and Experimental Medicine, University of Perugia, Via del Giochetto, 06100 Perugia, Italy. riccardi@unipg.it
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Migliorati
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D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation; D053450:Glucocorticoid-Induced TNFR-Related Protein; D005938:Glucocorticoids / Q000494:pharmacology; D016350:Leucine Zippers; D018448:Models, Immunological; D008969:Molecular Sequence Data; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects*; D014157:Transcription Factors / Q000378:metabolism*
D053450:Glucocorticoid-Induced TNFR-Related Protein; D005938:Glucocorticoids; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human; C404226:TSC22D3 protein, human; D014157:Transcription Factors; D003907:Dexamethasone