Modulation of Pro- and Antiapoptotic Molecules in Double-positive (Cd4+cd8+) Thymocytes Following Dexamethasone Treatment.
From: Dipartimento di Medicina Clinica e Sperimentale, Sezione di Farmacologia, Tossicologia e Chemioterapia, Università di Perugia, Istituto di Biotecnologie Trapiantologiche and Polo Scientifico e Didattico di Terni, Perugia, Italy.
The Journal of pharmacology and experimental therapeutics
- Publish Date: Nov 2006
- ISSN: 0022-3565
- Volume: 319
- Issue: 2
- Pages: 887-97
- Medium: Print
- Language: English
- Citation (JAMA): Bianchini Rodolfo, Nocentini Giuseppe, Krausz Ludovic Tibor, et al. Modulation of Pro- and Antiapoptotic Molecules in Double-positive (Cd4+cd8+) Thymocytes Following Dexamethasone Treatment.. J. Pharmacol. Exp. Ther. Nov 2006;319:887-97
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 h 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 polymerase chain reaction. In particular, dexamethasone caused down-regulation of genes promoting DP thymocyte survival (e.g., Notch1, suppressor of cytokine signaling 1, and inhibitor of DNA binding 3) or modulation of genes activating cell death through the ceramide pathway (UDP-glucose ceramide glucosyltransferase, sphingosine 1-phosphate phosphatase, dihydroceramide desaturase, isoform 1, and G protein-coupled receptor 65) or through the mitochondrial machinery. Among the latter, there are Bcl-2 family members (Bim, Bfl-1, Bcl-xL, and Bcl-xbeta), genes involved in the control of redox status (thioredoxin reductase, thioredoxin reductase inhibitor, and NADP(+)-dependent isocitrate dehydrogenase) and genes belonging to Tis11 family that 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.
Mesh Headings (Keywords): Animals, Antigens, CD4, Antigens, CD8, Apoptosis, Dexamethasone, Gene Expression Regulation, Genes, bcl-2, Mice, Mice, Inbred C3H, RNA Stability, Reactive Oxygen Species, Sphingomyelins, T-Lymphocytes
Check for Full Text / PubMed Unique Identifier (PMID): 16914556
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.