NITRIC-OXIDE IN HUMAN SKIN - CURRENT STATUS AND FUTURE-PROSPECTS

The gaseous free radical nitric oxide is an important biologic mediato r with physiologic and pathophysiologic roles in nearly every organ sy stem. Because of its unique biologic activity, unusual chemical struct ure, and unprecedented mechanisms of action, nitric oxide, arguably mo re than any other natural product, has opened new avenues to investiga te cellular processes. Nitric oxide is generated in biologic tissues b y specific nitric oxide synthases that metabolize arginine and molecul ar oxygen to citrulline and nitric oxide. Besides its function as a di ffusible messenger in the vasculature and in neurons, nitric oxide als o plays a key role in innate immunity and inflammation. Recent progres s has allowed the identification of the nitric oxide pathway in severa l cell types that reside in the skin, including keratinocytes, melanoc ytes, Langerhans cells, fibroblasts, and endothelial cells. Convincing evidence suggests that nitric oxide synthesis in these cells can be m odulated by calcium-mobilizing agonists as well as diverse inflammator y and immune stimuli, and thereby contributes to the pathogenesis of s everal human skin diseases. Characterization of these intrinsic and ex trinsic regulatory stimuli of nitric oxide synthesis has afforded subs tantial insights into the role of nitric oxide in inflammatory, hyperp roliferative, and autoimmune skin diseases, as well as skin cancer, an d may ultimately form the basis for future therapeutic intervention. T he demonstrable and potential roles of nitric oxide in skin disease pa thogenesis and treatment are the subjects of this review.