Glucocorticoid-Induced Leucine Zipper (GILZ) Over-Expression in T Lymphocytes Inhibits Inflammation and Tissue Damage in Spinal Cord Injury

Emanuela Esposito, Stefano Bruscoli, Emanuela Mazzon, Irene Paterniti, Maddalena Coppo, Enrico Velardi, Salvatore Cuzzocrea, Carlo Riccardi

Research output: Contribution to journalArticlepeer-review

Abstract

Spinal cord injury (SCI) is a traumatic event that causes a secondary and extended inflammation characterized by infiltration of immune cells, including T lymphocytes, release of pro-inflammatory mediators in the lesion site, and tissue degeneration. Current therapeutic approaches for SCI are limited to glucocorticoids (GC) due to their potent anti-inflammatory activity. GC efficacy resides, in part, in the capability to inhibit NF-κB, T lymphocyte activation, and the consequent cytokine production. In this study, we performed experiments aimed to test the susceptibility of glucocorticoid-induced leucine zipper (GILZ) transgenic (GILZ TG) mice, in which GILZ is selectively over-expressed in T lymphocytes, to SCI induction. Consistent with a decreased inflammatory response, GILZ TG were less susceptible to SCI as compared to wild-type littermates. Notably, inhibition of NF-κB activation and nuclear translocation, diminished T lymphocytes activation and tissue infiltration, as well as decreased release of cytokines were evident in GILZ TG as compared to wild-type mice. Moreover, GILZ TG showed a reduced tumor necrosis factor-α, IL-1β, Inductible nitric oxide synthase (iNOS) and nytrotyrosine production, apoptosis, and neuronal tissue damage. Together these results indicate that GILZ mimics the anti-inflammatory effect of GC and represents a potential pharmacological target for modulation of T lymphocyte-mediated immune response in inflammatory disorders, such as SCI.

Original languageEnglish
Pages (from-to)210-225
Number of pages16
JournalNeurotherapeutics
Volume9
Issue number1
DOIs
Publication statusPublished - Jan 2012

Keywords

  • apoptosis
  • Glucocorticoid-induced leucine zipper
  • glucocorticoids
  • inflammation
  • spinal cord injury
  • T lymphocytes

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Clinical Neurology
  • Pharmacology

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