title: Astaxanthin attenuates the UVB-induced secretion of prostaglandin E2 and interleukin-8 in human keratinocytes by interrupting MSK1 phosphorylation in a ROS depletion-independent manner.
abstract: To elucidate the effects of redox balance regulation on cutaneous inflammation, we used the potent antioxidant astaxanthin (AX) to assess its effect on the UVB-induced secretion of PGE(2) and IL-8 in human keratinocytes and analysed its biological mechanism of action. The addition of AX (at 8 μm) to human keratinocytes even after UVB irradiation significantly down-regulated the increased secretion of PGE(2) or IL-8. Those suppressive effects were accompanied by significantly decreased expression of genes encoding COX-2 or IL-8 as well as COX-2 protein. Analysis using a specific NF-κB tanslocation inhibitor demonstrated that the UVB-stimulated secretion of PGE(2) and IL-8 was significantly abolished by its treatment prior to UVB irradiation. Western blotting of phosphorylated signalling molecules revealed that UVB irradiation (80 mJ/cm(2) ) significantly stimulated the phosphorylation of p38, ERK and JNK, which was not suppressed by treatment with AX after irradiation. In contrast, AX significantly inhibited the UVB-increased phosphorylation of mitogen- and stress-activated protein kinase (MSK)-1, NF-kBp65 or CREB even when treated postirradiation. Further, the MSK1 inhibitor H89 significantly down-regulated the increased secretion of PGE(2) and IL-8 in UVB-exposed human keratinocytes, following post-irradiation treatment. These findings suggests that AX attenuates the auto-phosphorylation of MSK1 required for its activation, which results in the decreased phosphorylation of NF-kBp65, which in turn probably leads to a deficiency of NF-kB DNA binding activity. This may be associated with the significant suppression of PGE(2) /IL-8 secretion via the down-regulated expression of COX-2 and IL-8 at the gene and/or protein levels.
authors.affiliation: School of Bioscience and Biotechnology, Tokyo University of Technology, Hachioji, Tokyo, Japan. kimura@nagahp.jp
authors.forename: Shuko
authors.initials: S
authors.lastname: Terazawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nakajima
authors.forename: Mori
authors.initials: M
authors.lastname: Shingo
authors.forename: Takao
authors.initials: T
authors.lastname: Niwano
authors.forename: Genji
authors.initials: G
authors.lastname: Imokawa
mesh_terms: D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D018613:Microscopy, Confocal / Q000379:methods; D008954:Models, Biological; D010766:Phosphorylation; D017382:Reactive Oxygen Species; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism*; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology; D014466:Ultraviolet Rays; D024341:Xanthophylls / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D016209:Interleukin-8; D007546:Isoquinolines; D017382:Reactive Oxygen Species; D013449:Sulfonamides; D024341:Xanthophylls; C005948:astaxanthine; D051546:Cyclooxygenase 2; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1; D015232:Dinoprostone; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide