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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.
AuthorsJe Won Ko, Sei Young Lim, Kwang Chul Chung, Joo Weon Lim, Hyeyoung Kim
JournalThe international journal of biochemistry & cell biology (Int J Biochem Cell Biol) Vol. 55 Pg. 164-70 (Oct 2014) ISSN: 1878-5875 [Electronic] Netherlands
PMID25218171 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Ltd. All rights reserved.
Chemical References
  • Chelating Agents
  • DNA-Binding Proteins
  • Free Radical Scavengers
  • Interleukin-1beta
  • Interleukin-8
  • Intracellular Signaling Peptides and Proteins
  • Muscle Proteins
  • NF-kappa B
  • RCAN1 protein, human
  • Reactive Oxygen Species
  • SOD1 protein, human
  • Egtazic Acid
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Calcium
  • Acetylcysteine
Topics
  • Acetylcysteine (pharmacology)
  • Blotting, Western
  • Calcium (metabolism)
  • Chelating Agents (pharmacology)
  • DNA-Binding Proteins
  • Egtazic Acid (analogs & derivatives, pharmacology)
  • Free Radical Scavengers (pharmacology)
  • Gene Expression (drug effects)
  • HEK293 Cells
  • Humans
  • Interleukin-1beta (pharmacology)
  • Interleukin-8 (genetics, metabolism)
  • Intracellular Signaling Peptides and Proteins (genetics, metabolism)
  • Intracellular Space (drug effects, metabolism)
  • Microscopy, Confocal
  • Mitochondria (drug effects, metabolism)
  • Muscle Proteins (genetics, metabolism)
  • NF-kappa B (metabolism)
  • Reactive Oxygen Species (metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Superoxide Dismutase (genetics, metabolism)
  • Superoxide Dismutase-1
  • Transfection

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