Glucocorticoid-induced leucine zipper (GILZ) controls inflammation and tissue damage after spinal cord injury.

Abstract

Spinal cord injury (SCI) occurs following damage to the spinal column. Following trauma, tissue damage is further exacerbated by a secondary damage due to a SCI-activated inflammatory process. Control of leukocytes activity is essential to therapeutic inhibition of the spinal cord damage to ameliorate the patient's conditions. The mechanisms that regulate neuroinflammation following SCI, including T-cell infiltration, have not been completely clarified. Glucocorticoids (GC) are antiinflammatory drugs widely used in therapy, including treatment of SCI. GC efficacy may be linked to many molecular mechanisms that are involved in regulation of leukocytes migration, activation, and differentiation. We have previously shown that the antiinflammatory activity of GC is in part mediated by glucocorticoid-induced leucine zipper (GILZ). Here, we investigated the role of GILZ in inflammation and spinal cord tissue damage following a spinal trauma. We address the role of GILZ in SCI-induced inflammation and tissue damage using a model of SCI in gilz knockout (gilz KO) and wild-type (WT) mice. We found that GILZ deficiency is associated with a strong reduction of SCI-induced inflammation and a significantly reduced lesion area following SCI. These results demonstrate that GILZ is involved in induction of neuroinflammation and functional outcomes of spinal cord trauma.