Various glucocorticoids differ in their ability to induce gene expression,apoptosis and to repress NF-kappa B-dependent transcription

Glucocorticoids (GCs) influence a great variety of cellular functions by at least three important modes of action: the activation (sr repression) of g enes controlled by binding sites for the glucocorticoid receptor (GR), the induction of apoptosis in lymphocytes and the recently discovered cross-tal k to other transcription factors such as NF-kappa B. In this study we syste matically compared various natural and synthetic steroid hormones frequentl y used as therapeutic agents on their ability to mediate these three modes of action. Betamethasone, triamcinolone, dexamethasone and clobetasol turne d out to be the best inducers of gene expression and apoptosis, All GCs inc luding the antagonistic compound RU486 efficiently reduced NF-kappa B-media ted transactivation to comparable extents, suggesting that ligand-induced n uclear localization of the GR is sufficient for transrepression, Glucocorti coid treatment of cells did not result in elevated I kappa B-alpha expressi on, but impaired the tumor necrosis factor (TNF)-alpha-induced degradation of I kappa B-a alpha without affecting DNA binding of NF-kappa B, The struc tural requirements for the various functions of glucocorticoids are discuss ed. (C) 1998 Federation of European Biochemical Societies.