PMID- 23165982 OWN - NLM STAT- MEDLINE DCOM- 20130503 LR - 20121127 IS - 1791-244X (Electronic) IS - 1107-3756 (Linking) VI - 31 IP - 1 DP - 2013 Jan TI - Involvement of Nrf2 activation in the upregulation of S100A9 by exposure to inorganic arsenite. PG - 259-64 LID - 10.3892/ijmm.2012.1185 [doi] AB - 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. FAU - Sumi, Daigo AU - Sumi D AD - Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan. FAU - Shimizu, Yuri AU - Shimizu Y FAU - Himeno, Seiichiro AU - Himeno S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121116 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (Arsenites) RN - 0 (Calgranulin A) RN - 0 (Calgranulin B) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NFE2L2 protein, human) RN - 0 (Sodium Compounds) RN - 48OVY2OC72 (sodium arsenite) SB - IM MH - Arsenites/*toxicity MH - Calgranulin A/genetics/metabolism MH - Calgranulin B/genetics/*metabolism MH - Cell Line, Tumor MH - Epithelial Cells/drug effects/pathology MH - Humans MH - Keratinocytes/cytology/metabolism/*pathology MH - NF-E2-Related Factor 2/*genetics/metabolism MH - Promoter Regions, Genetic MH - Sodium Compounds/*toxicity MH - *Transcriptional Activation MH - Up-Regulation MH - Urothelium/drug effects/pathology EDAT- 2012/11/21 06:00 MHDA- 2013/05/04 06:00 CRDT- 2012/11/21 06:00 PHST- 2012/08/23 00:00 [received] PHST- 2012/10/19 00:00 [accepted] PHST- 2012/11/21 06:00 [entrez] PHST- 2012/11/21 06:00 [pubmed] PHST- 2013/05/04 06:00 [medline] AID - 10.3892/ijmm.2012.1185 [doi] PST - ppublish SO - Int J Mol Med. 2013 Jan;31(1):259-64. doi: 10.3892/ijmm.2012.1185. Epub 2012 Nov 16.