title: Involvement of Nrf2 activation in the upregulation of S100A9 by exposure             to inorganic arsenite.
abstract: This study examined whether S100A8 and S100A9, which comprise a complex             called calprotectin, are upregulated by exposure to sodium arsenite [As(III)]             in nine lines of human-derived cells. HaCaT skin keratinocyte cells, U937 leukemic             monocyte cells, and UROtsa urothelial cells showed increased mRNA levels of S100A8             and S100A9 after a 2-week exposure to As(III). To understand the mechanisms regulating             S100A9 upregulation in response to As(III), we tested S100A9 promoter-dependent             luciferase activity in HaCaT cells transfected with S100A9 promoter (-1000/+429)-fused             luciferase cDNA. The results indicated that exposure to As(III) stimulated S100A9             promoter-dependent luciferase activity. In addition, the transcription NF-E2-related             factor 2 (Nrf2) was strongly activated in HaCaT cells exposed to As(III). Since             two putative antioxidant response elements were found in the S100A9 promoter (ARE1,             5'-ACAGGCAGGG-3' from -897 to -887; ARE2, 5'-ATCTTCCGGAG-3' from -78 to -67),             we constructed deletion mutants of each ARE on S100A9 promoter-fused luciferase             cDNA. The results indicated that ARE2 is the responsible element for the activation             of S100A9 transcription in response to As(III). This report is the first to demonstrate             that As(III) enhanced S100A8 and S100A9 expression in human-derived cells and             As(III)-induced S100A9 expression is dependent on Nrf2 activation.
authors.affiliation: Laboratory of Molecular Nutrition and Toxicology, Faculty of                     Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima                     770-8514, Japan.
authors.forename: Daigo
authors.initials: D
authors.lastname: Sumi
authors.forename: Yuri
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Himeno
mesh_terms: D018053:Arsenites / Q000633:toxicity*; D040501:Calgranulin A / Q000235:genetics / Q000378:metabolism; D040502:Calgranulin B / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017670:Sodium Compounds / Q000633:toxicity*; D015533:Transcriptional Activation; D015854:Up-Regulation; D019459:Urothelium / Q000187:drug effects / Q000473:pathology
chemical_list: D018053:Arsenites; D040501:Calgranulin A; D040502:Calgranulin B; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017670:Sodium Compounds; C017947:sodium arsenite