Received for publication May 30, 2006.
Revised July 12, 2006.
Accepted for publication August 15, 2006.

Modulation of pro- and anti-apoptotic molecules in double positive (CD4⁺CD8⁺) thymocytes following dexamethasone treatment

Abstract

Glucocorticoids play a role in regulation of T lymphocytes homeostasis and development. In particular, glucocorticoid treatment induces massive apoptosis of CD4⁺CD8⁺ double positive (DP) thymocytes. This effect is due to many mechanisms, mainly driven by modulation of gene transcription. To find out which genes are modulated, we analyzed DP thymocytes treated for 3 hours with dexamethasone (a synthetic glucocorticoid), by global gene expression profiling. Results indicate modulation of 163 genes, also confirmed by either RNAse protection assay or Real Time PCR. In particular, dexamethasone caused down-regulation of genes promoting DP thymocyte survival (e.g. Notch1, Suppressor of cytokine signaling 1-Socs1 and Inhibitor of DNA binding 3-Id3) or modulation of genes activating cell death through the ceramide pathway (UDP-glucose ceramide glucosyltransferase-Ugcg, sphingosine 1-phosphate phosphatase-Sgpp1, dihydroceramide desaturase, isoform 1-Degs1 and G-protein-coupled receptor 65-Gpr65) or through the mithocondrial machinery. Among the latter, there are Bcl-2 family members (Bim, Bfl-1, Bcl-xL and Bcl-x), genes involved in the control of redox status (thioredoxin reductase, thioredoxin reductase inhibitor-Txnip and NADP⁺-dependent isocitrate dehydrogenase-Idh2) and genes belonging to Tis11 family which are involved in mRNA stability. Our study suggests that dexamethasone treatment of DP thymocytes modulates several genes belonging to apoptosis-related systems that can contribute to their apoptosis.

Key words: apoptosis, double positive thymocytes, gene profiling, gene trascription regulation, glucocorticoid hormones, microarray

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