title: IL-8 production and AP-1 transactivation induced by UVA in human keratinocytes: roles of D-alpha-tocopherol.
abstract: Identification of individual response-signal pathway induced by UVA-irradiation is necessary for understanding photo-biological and -pathological mechanisms with respect to the prevention of UV-irradiated skin damage and aging. Here, we investigated the role of D-alpha-tocopherol in the regulation of IL-8 production and AP-1 binding activity in UVA-irradiated human keratinocytes. UVA dramatically upregulated IL-8 mRNA expression and protein secretion and enhanced the AP-1-DNA binding activity. These effects of UVA irradiation were effectively reduced by D-alpha-tocopherol in a dose-dependent manner. The human keratinocytes expressed various NAD(P)H oxidase components, gp91phox homologues Nox1, and p22phox, p47phox, p67phox, as well as NOXO1, suggesting that cellular stress induced by UVA included the activation of non-phagocytic NADPH oxidase system, leading to AP-1 transactivation and IL-8 expression. D-alpha-tocopherol significantly inhibited the NADPH oxidase activity and the formation of malondialdehyde-thiobarbituric acid under UVA exposure. These results demonstrated that D-alpha-tocopherol may be able to prevent the IL-8 upregulation and the increase in AP-1 activation induced by UVA irradiation through down-modulating cellular oxidative stress.
authors.affiliation: Medicine Clinic III, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, Germany. shuling.wu@charite.de
authors.forename: Shuling
authors.initials: S
authors.lastname: Wu
authors.forename: Jianping
authors.initials: J
authors.lastname: Gao
authors.forename: Q Thai
authors.initials: QT
authors.lastname: Dinh
authors.forename: Christiane
authors.initials: C
authors.lastname: Chen
authors.forename: Sabine
authors.initials: S
authors.lastname: Fimmel
mesh_terms: D006801:Humans; D007231:Infant, Newborn; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000201:enzymology / Q000378:metabolism* / Q000528:radiation effects*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects / Q000528:radiation effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013858:Thiobarbiturates / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics*; D015533:Transcriptional Activation / Q000187:drug effects* / Q000528:radiation effects; D014466:Ultraviolet Rays; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D016209:Interleukin-8; D012333:RNA, Messenger; D013858:Thiobarbiturates; D018808:Transcription Factor AP-1; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D024502:alpha-Tocopherol