Reactive oxygen species mediate IL-8 expression in Down syndrome candidate region-1-overexpressed cells |
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| Institution: | 1. Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden;2. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden;3. Division of Biochemistry, Department of Medical Biochemistry and Biophysics all at Karolinska Institutet, Stockholm, Sweden;4. Dept of Cardiology, Karolinska University Hospital, Stockholm, Sweden;5. Division of Cardiovascular Medicine, Dept of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden;1. Department of Nephrology, Universitätsmedizin Charité Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany;2. Department of Pathology, Universitätsmedizin Charité Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany;3. Deutsches Rheuma-Forschungszentrum, Charitéplatz 1, 10117 Berlin, Germany;1. Dipartimento di Scienze Biomediche Sperimentali e Cliniche “Mario Serio,” Università di Firenze, Viale G.B. Morgagni 50, Firenze 50134, Italy;2. Istituto Interuniversitario di Miologia, Italy;3. Faculty of Mathematics and Natural Science, Institute of Nutritional Science, Department of Toxicology, University of Potsdam, Arthur-Scheunert Allee 114-116, Nuthetal, Potsdam 14558, Germany |
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| 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. |
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| Keywords: | Down syndrome critical region-1 Reactive oxygen species IL-8 NF-κB SOD1 |
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