ABSTRACT
1Dept. of Clinical and Experimental Medicine, Section of Pharmacology, University of Perugia, Italy.
2Dept. of Clinical Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy.
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-kB, T lymphocytes activation and the consequent cytokines production. In this study we performed experiments aimed to test the susceptibility of glucocorticoid induced leucine zipper (GILZ) transgenic (GILZTG) mice, in which GILZ is selectively over-expressed in T lymphocytes, to SCI induction. Consistent with a decreased inflammatory response, GILZTG were less susceptible to SCI as compared to wild type (WT) littermates. Of note, inhibition of NF-kB activation and nuclear translocation, diminished T lymphocytes infiltration and decreased release of cytokines, such as TNFaand IL-1b, were evident in GILZTG as compared to WT mice. Moreover, GILZTG showed a reduced iNOS and nytrotyrosine production, apoptosis and neuronal tissue damage.
Together these results here described demonstrate that GILZ, a mediator of GC anti-inflammatory activity, has a critical role in regulation of SCI development. Moreover, these observations further indicate CD4+ and CD8a+ T cells are important in SCI development and should represent an appropriate target for new therapeutic approaches. Finally, evaluation of GILZ expression in T lymphocytes, during pharmacological therapy with GC, could be a mean to monitor the drug-response and the therapy outcome of autoimmune/inflammatory diseases.