Lack of glucocorticoid-induced leucine zipper (GILZ) deregulates B-cell survival and results in B-cell lymphocytosis in mice

摘要: Glucocorticoids (GC) are widely used as antiinflammatory/immunosuppressive drugs and antitumor agents in several types of lymphoma leukemia. Therapeutic doses GC induce growth-suppressive cytotoxic effects on various leukocytes including B cells. Molecular mechanisms action include induction target genes. Glucocorticoid-induced leucine zipper (GILZ) is a rapidly, potently, invariably GC-induced gene. It mediates number effects, such control cell proliferation, differentiation, apoptosis. Here we show that deletion GILZ mice leads to an accumulation lymphocytes the bone marrow, blood, lymphoid tissues. Gilz knockout (KO) develop progressive nonlethal lymphocytosis, with expansion B220(+) cells marrow periphery, dependent increased B-cell survival. Decreased apoptosis lacking correlates NF-κB transcriptional activity Bcl-2 expression. cell-specific gilz KO confirmed effect self-intrinsic. These results establish important regulator survival suggest deregulation expression could be implicated pathogenesis disorders.