TY - JOUR
T1 - Glucocorticoid-Induced Leucine Zipper (GILZ) Over-Expression in T Lymphocytes Inhibits Inflammation and Tissue Damage in Spinal Cord Injury
AU - Esposito, Emanuela
AU - Bruscoli, Stefano
AU - Mazzon, Emanuela
AU - Paterniti, Irene
AU - Coppo, Maddalena
AU - Velardi, Enrico
AU - Cuzzocrea, Salvatore
AU - Riccardi, Carlo
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
KW - apoptosis
KW - Glucocorticoid-induced leucine zipper
KW - glucocorticoids
KW - inflammation
KW - spinal cord injury
KW - T lymphocytes
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U2 - 10.1007/s13311-011-0084-7
DO - 10.1007/s13311-011-0084-7
M3 - Article
C2 - 22125095
AN - SCOPUS:84856575653
VL - 9
SP - 210
EP - 225
JO - Neurotherapeutics
JF - Neurotherapeutics
SN - 1933-7213
IS - 1
ER -