The precise mechanism of the anti-inflammatory activity of topical steroids in the treatment of steroid-responsive dermatoses, in general, is uncertain. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2. Initially, however, clobetasol, like other corticosteroids, binds to the glucocorticoid receptor, which complexes, entrees the cell nucleus and modifies genetic transcription (transrepression/transactivation).
Receptor for glucocorticoids (GC). It has a dual-mode of action: a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA and as a modulator of other transcription factors. It affects inflammatory responses, cellular proliferation, and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic gene expression.