Figure 2

Genomic action of glucocorticoids. Glucocorticoid binds to the glucocorticoid receptor (GCR) in the cytoplasm. This complex migrates into the nucleus. Activation of transcription (transactivation) by binding of GCR-glucocorticoid complex dimers to glucocorticoid-responsive elements of DNA upregulates synthesis of regulatory proteins, thought to be responsible for metabolic effects and also some anti-inflammatory/ immunosuppressive effects. Interaction of GCR-glucocorticoid complex monomers with proinflammatory transcription factors, such as activator protein-1, interferon regulatory factor-3 and nuclear factor (NF)-κB, leads to inhibition of binding of these transcriptional factors to their DNA consensus sites (for NF-κB: NF-κB-responsive elements). The transcription of these proinflammatory transcription factors is thus repressed. This process is called transrepression and downregulates synthesis of predominantly inflammatory/immunosuppressive proteins. Adapted from [128].