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Given that many skin disorders have an immunologic basis or involve inflammatory reactions, compounds affecting the afferent or the effector limbs of immune responses play a central role in dermatologic therapy. Topical glu-cocorticosteroids (GCs) represent the mainstay of anti-inflammatory and im-munosuppressive treatment of inflammatory skin diseases. However, despite their broad and common usage, some mechanisms by which GCs exert their functions still remain obscure. It is thought that binding of a GC to a cyto-plasmic glucocorticosteroid receptor (GCR) [65] leads to dissociation of a complex composed of a GCR and two heat-shock proteins [51]. This dissociation is followed by migration of the GCR-GC complex into the nucleus and binding to specific DNA sites called glucocorticoid response elements (GC-REs). A number of genes have been identified that are regulated by GC-REs, including lipocortin-1, an inhibitor of phospholipase A2 [22]. In addition, there is evidence that GCs can directly inhibit phospholipase A2 [51]. Both direct and indirect effects on phospholipase A2 synergistically decrease mediators of inflammation such as thromboxanes, prostaglandins, and leuko-trienes, thus inhibiting leukocyte attraction to sites of inflammation [27, 28]. |
