title: Reactive oxygen species mediate IL-8 expression in Down syndrome candidate region-1-overexpressed cells.
abstract: Reactive oxygen species (ROS) have been considered to mediate inflammation in Down syndrome (DS). The present study is purposed to examine the mechanism of increased ROS levels and inflammatory cytokine IL-8 expression in Down syndrome candidate region-1 (DSCR1)-transfected cells, by determining ROS levels, IL-8 expression, NF-κB activation, and SOD1 levels in human embryonic kidney (HEK) 293 cells. The cells were treated with an antioxidant N-acetyl cysteine (NAC) or a calcium chelator BAPTA and stimulated with or without IL-1β. As a result, basal levels of ROS, IL-8, and NF-κB-DNA binding activity were higher, and basal SOD1 levels were higher in DSCR1-transfected cells than pcDNA-transfected cells. BAPTA and NAC inhibited increase in ROS (intracellular and mitochondrial levels) in DSCR-1-transfected cells without treatment of IL-1β. DSCR1 transfection-induced changes were increased by treatment with IL-1β, which was suppressed by NAC and BAPTA. Transfection of SOD1 inhibited ROS levels in DSCR1-transfected cells. In conclusion, ROS activate NF-κB and IL-8 induction in DSCR1-transfected cells in a calcium-dependent manner, which is augmented by IL-1β since IL-1β increases calcium and ROS levels in the cells. Reducing ROS levels by treatment of antioxidants may be beneficial for preventing DS-associated inflammation by suppressing cytokine expression.
authors.affiliation: Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Je Won
authors.initials: JW
authors.lastname: Ko
authors.affiliation: Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Sei Young
authors.initials: SY
authors.lastname: Lim
authors.affiliation: Department of Biology, College of Science, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Kwang Chul
authors.initials: KC
authors.lastname: Chung
authors.affiliation: Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Joo Weon
authors.initials: JW
authors.lastname: Lim
authors.affiliation: Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 120-749, Republic of Korea. Electronic address: kim626@yonsei.ac.kr.
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Kim
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D004268:DNA-Binding Proteins; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014162:Transfection
chemical_list: D002614:Chelating Agents; D004268:DNA-Binding Proteins; D016166:Free Radical Scavengers; D053583:Interleukin-1beta; D016209:Interleukin-8; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D016328:NF-kappa B; C108612:RCAN1 protein, human; D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D004533:Egtazic Acid; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D000111:Acetylcysteine
keywords: Down syndrome critical region-1; IL-8; NF-κB; Reactive oxygen species; SOD1