title: Protective role of nitric oxide-mediated inflammatory response against lipid peroxidation in ultraviolet B-irradiated skin.
abstract: Ultraviolet (UV) irradiation is known to induce serious oxidative damage in the skin via lipid peroxidation. Nitric oxide (NO) synthesized by keratinocytes, melanocytes and endothelial cells in response to proinflammatory cytokines 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 peroxidation in murine skin in vivo. UVB induced a dose-dependent increase in lipid peroxidation of skin extracts in vitro; however, lipid peroxidation in the 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). Time-delayed inhibition of lipid peroxidation in the skin in vivo was observed after irradiation at 1.5 J cm-2. Administration of N G-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, enhanced lipid peroxidation (P < 0.05), while it suppressed the ear-swelling response (ESR), a biological marker of inflammation. By contrast, administration of sodium nitroprusside, an NO enhancer, suppressed lipid peroxidation (P < 0. 01), while it enhanced the ESR. Expression of inducible nitric oxide synthase (iNOS) was observed from 12 to 48 h postirradiation at doses of 0.4-1.6 J cm-2. The 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-mediated inflammatory response in vivo.
authors.affiliation: Department of Dermatology, Chonnam University Medical School, 8 Hak-dong, Dong-ku, Kwangju 501-757, Korea. schul@chonnam.ac.kr
authors.forename: S C
authors.initials: SC
authors.lastname: Lee
authors.forename: J W
authors.initials: JW
authors.lastname: Lee
authors.forename: J E
authors.initials: JE
authors.lastname: Jung
authors.forename: H W
authors.initials: HW
authors.lastname: Lee
authors.forename: S D
authors.initials: SD
authors.lastname: Chun
authors.forename: I K
authors.initials: IK
authors.lastname: Kang
authors.forename: Y H
authors.initials: YH
authors.lastname: Won
authors.forename: Y P
authors.initials: YP
authors.lastname: Kim
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007249:Inflammation / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000502:physiology / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012867:Skin / Q000528:radiation effects; D013997:Time Factors; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D019331:NG-Nitroarginine Methyl Ester