Affordable Access

Publisher Website

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

Authors
Journal
FEBS Letters
0014-5793
Publisher
Wiley Blackwell (John Wiley & Sons)
Publication Date
Volume
441
Issue
3
Identifiers
DOI: 10.1016/s0014-5793(98)01609-3
Keywords
  • Glucocorticoid
  • Apoptosis
  • Nf-κB
  • Gene Expression
  • Cross-Talk
Disciplines
  • Medicine

Abstract

Abstract Glucocorticoids (GCs) influence a great variety of cellular functions by at least three important modes of action: the activation (or repression) of genes controlled by binding sites for the glucocorticoid receptor (GR), the induction of apoptosis in lymphocytes and the recently discovered cross-talk to other transcription factors such as NF-κB. In this study we systematically compared various natural and synthetic steroid hormones frequently used as therapeutic agents on their ability to mediate these three modes of action. Betamethasone, triamcinolone, dexamethasone and clobetasol turned out to be the best inducers of gene expression and apoptosis. All GCs including the antagonistic compound RU486 efficiently reduced NF-κB-mediated transactivation to comparable extents, suggesting that ligand-induced nuclear localization of the GR is sufficient for transrepression. Glucocorticoid treatment of cells did not result in elevated IκB-α expression, but impaired the tumor necrosis factor (TNF)-α-induced degradation of IκB-α without affecting DNA binding of NF-κB. The structural requirements for the various functions of glucocorticoids are discussed.

There are no comments yet on this publication. Be the first to share your thoughts.