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 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.
De Bosscher
K
K
Department of Molecular Biology, University of Gent and Flanders Interuniversity Institute for Biotechnology, K.L. Ledeganckstraat 35, 9000, Gent, Belgium.
Vanden Berghe
W
W
Haegeman
G
G
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D020672:I-kappa B Proteins; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000502:physiology; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
D000893:Anti-Inflammatory Agents; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D020672:I-kappa B Proteins; D007166:Immunosuppressive Agents; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D000072000:NF-KappaB Inhibitor alpha