Topical corticosteroids: mechanisms of action.
Corticosteroids modify the functions of epidermal and dermal cells and of leukocytes participating in proliferative and inflammatory skin diseases. After passage through the cell membrane corticosteroids react with receptor proteins in the cytoplasm to form a steroid-receptor complex. This complex moves into the nucleus, where it binds to DNA. The binding process then changes the transcription of messenger RNA (mRNA). Because mRNA acts as template for protein synthesis, corticosteroids can either stimulate or inhibit the synthesis of specific proteins. Thus corticosteroids are known to stimulate the production of a glycoprotein called lipocortin. The formed lipocortin inhibits the activity of phospholipase A2, which releases arachidonic acid, the precursor of prostanoids and leukotrienes, from phospholipids. In contrast, corticosteroids inhibit mRNA responsible for interleukin-1 formation. These actions of corticosteroids on arachidonic acid metabolism and interleukin-1 formation produce anti-inflammatory, immunosuppressive and anti-mitogenic effects. Although this theory based on protein synthesis may not explain all effects of corticosteroids, these examples illustrate that a specific action on the molecular level can explain some of the characteristic and typical pharmacological effects of topically applied corticosteroids. Additional studies of the mechanism of action of corticosteroids are warranted. Such studies will not only help to explain how corticosteroids work, but also create a background that is essential for the development of novel non-steroidal anti-inflammatory drugs.
Kragballe
K
K
Department of Dermatology, Marselisborg Hospital, University of Aarhus, Denmark.
D000287:Administration, Topical; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D017302:Annexins; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000187:drug effects; D015777:Eicosanoids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000494:pharmacology; D007801:Langerhans Cells / Q000187:drug effects; D010740:Phospholipases / Q000037:antagonists & inhibitors
D000305:Adrenal Cortex Hormones; D017302:Annexins; D002135:Calcium-Binding Proteins; D015777:Eicosanoids; D007375:Interleukin-1; D010740:Phospholipases