title: 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: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Torre Biologica, Policlinico Universitario, Messina, Italy.
authors: Emanuela
authors: E
authors: Esposito
authors: Stefano
authors: S
authors: Bruscoli
authors: Emanuela
authors: E
authors: Mazzon
authors: Irene
authors: I
authors: Paterniti
authors: Maddalena
authors: M
authors: Coppo
authors: Enrico
authors: E
authors: Velardi
authors: Salvatore
authors: S
authors: Cuzzocrea
authors: Carlo
authors: C
authors: Riccardi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D019938:Cyclin D1 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013119:Spinal Cord Injuries / Q000150:complications* / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016207:Cytokines; C498608:Dsip1 protein, mouse; D005904:Glial Fibrillary Acidic Protein; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D015232:Dinoprostone