Molecular mechanisms for anti-inflammatory actions and insensitivity of steroids

Steroidal anti-inflammatory drugs (steroids) are used for atopic dermatitis and several intractable diseases. As well as natural glucocorticoids, steroids exert their actions by binding to glucocorticoid receptor (GR). The steroid-binding GR translocates into nuclear and regulates gene expression. Steroids induce the expression of anti-inflammatory proteins and inhibit that of inflammatory proteins such as cytokines/chemokines and inducible enzymes. GR binds to the specific DNA sequences, called glucocorticoid response element (GRE) or negative GRE on target genes to regulate the expression. In addition, the GR inhibits the activity of other transcription factors via tethering to them. Steroid resistance is induced by enhanced inflammatory responses via phosphorylation and degradation of GR and via induction of other transcription factors. Physicians and pharmacists should understand the molecular mechanisms of actions and insensitivity of steroids to avoid side-effects of steroids.