title: Marginal selenium deficiency down-regulates inflammation-related genes in splenic leukocytes of the mouse.
abstract: Moderate selenium deficiency may lead to an impaired capacity to cope with health challenges. Functional effects of suboptimal selenium intake are not fully known, and biomarkers for an insufficient selenium supply are inadequate. We therefore fed mice diets of moderately deficient or adequate selenium intake for 6 weeks. Changes in global gene expression were monitored by microarray analysis in splenic leukocytes. Genes for four selenoproteins, Sepw1, Gpx1, Selh and Sep15, were the most significantly down-regulated in moderate selenium deficiency, and this was confirmed by quantitative polymerase chain reaction (qPCR). Classification of significantly affected genes revealed that processes related to inflammation, heme biosynthesis, DNA replication and transcription, cell cycle and transport were affected by selenium restriction. Down-regulation by moderate selenium deficiency of specific genes involved in inflammation and heme biosynthesis was confirmed by qPCR. Myeloperoxidase and lysozyme activities were decreased in selenium-restricted leukocytes, providing evidence for functional consequences. Genes for 31 nuclear factor (NF)-κB targets were down-regulated in moderate selenium deficiency, indicating an impaired NF-κB signaling. Together, the observed changes point to a disturbance in inflammatory response. The selenoproteins found here to be sensitive to selenium intake in murine leukocytes might also be useful as biomarkers for a moderate selenium deficiency in humans.
authors.affiliation: Department Biochemistry of Micronutrients, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. annakipp@dife.de
authors.forename: Anna P
authors.initials: AP
authors.lastname: Kipp
authors.forename: Antje
authors.initials: A
authors.lastname: Banning
authors.forename: Evert M
authors.initials: EM
authors.lastname: van Schothorst
authors.forename: Catherine
authors.initials: C
authors.lastname: Méplan
authors.forename: Susan L
authors.initials: SL
authors.lastname: Coort
authors.forename: Chris T
authors.initials: CT
authors.lastname: Evelo
authors.forename: Jaap
authors.initials: J
authors.lastname: Keijer
authors.forename: John
authors.initials: J
authors.lastname: Hesketh
authors.forename: Regina
authors.initials: R
authors.lastname: Brigelius-Flohé
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012643:Selenium / Q000097:blood / Q000172:deficiency* / Q000378:metabolism / Q000627:therapeutic use; D051151:Selenoprotein W / Q000235:genetics / Q000378:metabolism; D051140:Selenoproteins / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index; D013154:Spleen / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation; D000094765:Glutathione Peroxidase GPX1
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; C495241:Selenof protein, rat; D051151:Selenoprotein W; D051140:Selenoproteins; C577619:selenoprotein H, rat; D009195:Peroxidase; D005979:Glutathione Peroxidase; D009113:Muramidase; D012643:Selenium; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse