Glucocorticoid hormones in the regulation of cell death

The immune T-cell compartment maintains the capability to respond to a wide variety of antigens (Ag). This whole process is regulated. by lymphocyte a poptosis (programmed cell death, PCD) and involves the coordinated expressi on of a great number of genes including those coding for cytokines and thei r receptors, such as for example IL-2/IL-2R and the Fas/FasL systems and th ose coding for transcription factors, including the NF-kB complex, involved in T-cell activation and apoptosis in that they simultaneously activate ce ll suicide and an anti-death programme. This binary effect, PCD activation and inhibition, is due on one hand to GCH-induced activation of the caspase s cascade and on the other to the induction of expression of a new gene tha t we have named GILZ. In fact, GILZ over-expression in transfected cells in hibits the sequential increase of NF-kB/DNA-binding activity, IL-2 producti on and IL-2R expression, and transcription of the Fas/FasL complex that fol lows TCR triggering and plays an important role in the control of T-lymphoc yte apoptosis. These results indicate a new mechanism responsible for the G CH-mediated inhibition of T-cell death and activation that could contribute to anti-inflammatory and immunosuppressive efficacy.