Protective role of nitric oxide-mediated inflammatory response against lipid peroxidation in ultraviolet B-irradiated skin

Ultraviolet (UV) irradiation is known to induce serious oxidative damage in the skin via lipid peroxidation. Nitric oxide (NO) synthesized by keratino cytes, melanocytes and endothelial cells in response to proinflammatory cyt okines and UV radiation, has been reported to prevent UV-induced apoptosis in the skin, We have examined the effects of NO on UVB-induced lipid peroxi dation in murine skin in vivo. WE induced a dose-dependent increase in lipi d peroxidation of skin extracts in vitro; however, lipid peroxidation in th e skin in vivo remained unaffected at irradiation doses of less than 1.0 J cm(-2) and decreased significantly at doses over 1.5 J cm(-2) (P < 0.01). T ime-delayed inhibition of lipid peroxidation in the skin in vivo was observ ed after irradiation at 1.5 J cm(-2) Administration of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, enhanced lipid peroxid ation (P < 0.05), while it suppressed the ear-swelling response (ESR), a bi ological marker of inflammation, By contrast, administration of sodium nitr oprusside, an NO enhancer, suppressed lipid peroxidation (P < 0.01), while it enhanced the ESR. Expression of inducible nitric oxide synthase (iNOS) w as observed from 12 to 48 h postirradiation at doses of 0.4-1.6 J cm(-2). T he UVB-induced iNOS expression was markedly inhibited by L-NAME, suggesting that iNOS is a major enzyme in the production of NO. These results suggest that NO acts as a mediator of the inflammatory response in UVB-irradiated skin, and that lipid peroxidation is inversely regulated with the NO-mediat ed inflammatory response in vivo.