A new dexamethasone-induced gene of the leucine zipper family protects T lymphocytes from TCR/CD3-activated cell death
Open accessAbstract
By comparing mRNA species expressed in dexamethasone (DEX)-treated and untreated murine thymocytes, we have identified a gene, glucocorticoid-induced leucine zipper (GILZ), encoding a new member of the leucine zipper family. GILZ was found expressed in normal lymphocytes from thymus, spleen, and lymph nodes, whereas low or no expression was detected in other nonlymphoid tissues, including brain, kidney, and liver. In thymocytes and peripheral T cells, GILZ gene expression is induced by DEX. Furthermore, GILZ expression selectively protects T cells from apoptosis induced by treatment with anti-CD3 monoclonal antibody but not by treatment with other apoptotic stimuli. This antiapoptotic effect correlates with inhibition of Fas and Fas ligand expression. Thus, GILZ is a candidate transcription factor involved in the regulation of apoptosis of T cells.
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GR-mediated transactivation typically induces expression of signaling inhibitors such as IκBα, MPK-1, IL-10, Annexin A1, GILZ, and SOCS proteins, which interfere with immune signaling pathways such as those triggered by Toll-like receptors.
“GR-mediated transactivation typically induces the expression of potent signaling inhibitors (e.g., IκBα, MPK-1, IL-10, Annexin A1, GILZ, and SOCS proteins), which strongly interfere with salient immune signaling pathways such as those triggered by the Toll-like receptors (TLR) (82–85).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [84]
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References 52 · Cited by 444
- Authors
- D'Adamio, F., Zollo, O., Moraca, R., Ayroldi, E., Bruscoli, S., Bartoli, A., Cannarile, L., Migliorati, G., & Riccardi, C.
- Affiliations
- University of Perugia (IT)
- Corresponding author
- Riccardi, Carlo
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 1997-12
- Volume
- 7
- Issue
- 6
- Pages
- 803-812
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2063861465
- Cited by
- 444
- References
- 52
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 10 · 2023: 8 · 2022: 9 · 2021: 15 · 2020: 18 · 2019: 30 · 2018: 23 · 2017: 15 · 2016: 18 · 2015: 14 · 2014: 25 · 2013: 19 · 2012: 23
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Associazione Italiana per la Ricerca sul Cancro
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- GILZ, dexamethasone, leucine zipper transcription factors, T cell apoptosis, anti-CD3 antibody, Fas, Fas ligand, glucocorticoid induction, thymocytes, T cell survival
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Cell Line, Dexamethasone, Membrane Glycoproteins, Mice, Inbred C3H, Molecular Sequence Data, Subcellular Fractions, T-Lymphocytes, Tissue Distribution, Transfection, Ultraviolet Rays, Gene Expression, Leucine Zippers, Apoptosis, Receptor-CD3 Complex, Antigen, T-Cell, DNA, Complementary, fas Receptor, Mice, Fas Ligand Protein
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