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

J Neuroimmunol. 2000 Sep 1;109(1):16-22. doi: 10.1016/s0165-5728(00)00297-6.

Abstract

Glucocorticoids are the most widely used anti-inflammatory and immunomodulatory agents, whose mechanism of action is based mainly on interference with the activity of transcription factors, such as nuclear factor kappaB (NF-kappaB) and activator protein-1 (AP-1). The precise molecular mechanisms of gene repression by glucocorticoids are a controversial matter, due to the existence of many conflicting hypotheses. We discuss the three main paradigms reported in the literature, namely the inhibitor kappaB-alpha (IkappaB-alpha) upregulatory model, the protein-protein interaction model and the competition model.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cyclic AMP Response Element-Binding Protein / physiology
  • DNA-Binding Proteins / physiology
  • Glucocorticoids / pharmacology*
  • Humans
  • I-kappa B Proteins*
  • Immunosuppressive Agents / pharmacology*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / physiology
  • Receptors, Glucocorticoid / physiology*
  • Transcription Factors / physiology*

Substances

  • Anti-Inflammatory Agents
  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • Glucocorticoids
  • I-kappa B Proteins
  • Immunosuppressive Agents
  • NF-kappa B
  • NFKBIA protein, human
  • Receptors, Glucocorticoid
  • Transcription Factors
  • NF-KappaB Inhibitor alpha