Glucocorticoid hormone-induced modulation of gene expression and regulation of T-cell death: role of GITR and GILZ, two dexamethasone-induced genes

Cell Death Differ. 1999 Dec;6(12):1182-9. doi: 10.1038/sj.cdd.4400609.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Dexamethasone / pharmacology*
  • Gene Expression Regulation
  • Glucocorticoid-Induced TNFR-Related Protein
  • Glucocorticoids / pharmacology
  • Leucine Zippers
  • Models, Immunological
  • Molecular Sequence Data
  • Receptors, Nerve Growth Factor / metabolism*
  • Receptors, Tumor Necrosis Factor / metabolism*
  • T-Lymphocytes / drug effects*
  • Transcription Factors / metabolism*

Substances

  • Glucocorticoid-Induced TNFR-Related Protein
  • Glucocorticoids
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • TNFRSF18 protein, human
  • TSC22D3 protein, human
  • Transcription Factors
  • Dexamethasone

Associated data

  • GENBANK/AF024519
  • GENBANK/U82534