Topical glucocorticoids and the skin--mechanisms of action: an update.
The topical glucocorticoids (GCs) represent the treatment of choice for many types of inflammatory dermatoses. Despite the extensive use of this class of drugs as first line therapy the mechanism of their action is uncertain. It is clear that the multiplicity of actions of the topical GCs is an important facet of their scope in the treatment of dermal disorders. The aim of this update is to review past and current theories regarding how these agents might work. Current understanding of the molecular mechanisms of GC action has advanced significantly over the past decade with the realisation that multiple systems are responsible for transduction of GC effects at a molecular level. The two primary modes of action are via interaction directly with DNA or indirectly through modulation of specific transcription factors: the endpoint in both cases being modulation of specific protein synthesis. Both of these mechanisms will be discussed. In particular this review will concentrate on the possibility that a GC-inducible protein, termed lipocortin 1, may have a significant role to play in the anti-inflammatory actions of these drugs. Additionally it has become apparent that several inflammatory enzymes induced in inflammation are sites of inhibitory action of the GCs, and the possibility that this occurs in the skin will be discussed paying particular attention to the inducible phospholipase A2, nitric oxide synthase and cyclooxygenase systems.
Ahluwalia
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Centre for Clinical Pharmacology, University College London, The Rayne Institute, UK. a.ahluwalia@ucl.ac.uk
D000287:Administration, Topical; D017305:Annexin A1 / Q000037:antagonists & inhibitors; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors; D005938:Glucocorticoids; D006801:Humans; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D012871:Skin Diseases / Q000188:drug therapy*
D017305:Annexin A1; D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D019001:Nitric Oxide Synthase; D010741:Phospholipases A; D054467:Phospholipases A2