Glucocorticoid-induced leucine zipper (GILZ) over-expression in T lymphocytes inhibits inflammation and tissue damage in spinal cord injury.

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.

• Authors: Emanuela Esposito, Stefano Bruscoli, Emanuela Mazzon, Irene Paterniti, Maddalena Coppo, Enrico Velardi, Salvatore Cuzzocrea, Carlo Riccardi
• Journal: Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics (Neurotherapeutics) Vol. 9 Issue 1 Pg. 210-25 (Jan 2012) ISSN: 1878-7479 [Electronic] United States
• PMID: 22125095 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Dsip1 protein, mouse
• Glial Fibrillary Acidic Protein
• Transcription Factors
• bcl-2-Associated X Protein
• Cyclin D1
• Peroxidase
• Nitric Oxide Synthase Type II
• Dinoprostone

Topics

• Animals
• Apoptosis (genetics)
• Cyclin D1 (metabolism)
• Cytokines (metabolism)
• Dinoprostone (metabolism)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Gene Expression Regulation (genetics, physiology)
• Glial Fibrillary Acidic Protein (metabolism)
• In Situ Nick-End Labeling
• Inflammation (etiology, genetics, metabolism, pathology)
• Mice
• Mice, Transgenic
• Nitric Oxide Synthase Type II (metabolism)
• Peroxidase (metabolism)
• Signal Transduction (genetics)
• Spinal Cord Injuries (complications, pathology)
• T-Lymphocytes (metabolism)
• Transcription Factors (genetics, metabolism)
• bcl-2-Associated X Protein (metabolism)