Mechanisms of anti-inflammatory action and of immunosuppression by glucocorticoids: negative interference of activated glucocorticoid receptor with transcription factors

Glucocorticoids are the most widely used anti-inflammatory and immunomodula tory agents, whose mechanism of action is based mainly on interference with the activity of transcription Factors, such us nuclear factor kappa B (NF- kappa B) and activator protein-1 (AP-1). The precise molecular mechanisms o f gene repression by glucocorticoids are a controversial matter, due to the existence of many conflicting hypotheses. We discuss the three main paradi gms reported in the literature, namely the inhibitor kappa B-alpha (I kappa B-alpha) upregulatory model, the protein-protein interaction model and the competition model. (C) 2000 Elsevier Science BN. All rights reserved.