ABSTRACT
PhD School in Pharmacological Biotechnology and Clinical Pharmacology.
Dept. of Clinical and Experimental Medicine, Section of Pharmacology, University of Perugia, Italy
Glucocorticoids (GC) are of extraordinary therapeutic value in a wide range of inflammatory, autoimmune and inflammatory diseases. Their therapeutic activity is due to regulatory effects on activation, cell growth and differentiation in a number of cells and tissues, including cells the immune/inflammatory system.
With the aim to deeply analyze the molecular mechanisms of GC action, we have identified a number of GC-induced genes including GILZ (Glucocorticoid-Induced Leucine Zipper), a protein rapidly induced by GC treatment. Using different experimental models of inflammatory diseases, we show GILZ is an important mediator of the anti-inflammatory and immunosuppressive effects of GC. Moreover, we identified a new GILZ isoform, L-GILZ, involved in mediating the effects of GC on inflammation and on cell differentiation. Furthermore, our study demonstrates that both GILZ and L-GILZ are crucial mediators of GC-induced effects in that mediate the anti-inflammatory/immunosuppressive activity. In particular, GILZ regulates T cell activation and differentiation, cytokines, including pro-inflammatory cytokines, production and inflammatory process development.
Results could provide new means to predict sensitivity of normal and tumor cells to treatment with GC and to outline new therapeutic approaches.