title: Effect of oxidative stress on respiratory epithelium from children with Down syndrome.
abstract: Children with Down syndrome are at high risk for acute respiratory distress syndrome. In Down syndrome, both regulation of inflammation and apoptosis, important in acute respiratory distress syndrome pathophysiology, are abnormal. This has been linked to an imbalance in free radical scavengers. We investigated the expression of free radical scavengers and the effect of oxidative stress in terms of apoptosis and inflammation in respiratory epithelium from children with Down syndrome compared with control subjects. We cultured primary nasal epithelial cells from Down syndrome children (n=12) and controls (n=17) and exposed them to oxidative stress by supplementing superoxide. First we showed that the expression of the free radical scavengers CuZn-superoxide dismutase was 28% higher (p=0.06), catalase was 36% lower (p=0.04) and glutathione peroxidase was 73% lower (p=0.004) in Down syndrome children compared with controls. We found no significant difference in apoptosis, between Down syndrome and control subjects after exposure to oxidative stress. We also found no significant difference in levels of interleukin (IL)-1β, IL-6, IL-8, vascular endothelial growth factor and granulocyte colony-stimulating factor in primary nasal epithelial cell supernatant after exposure to oxidative stress between Down syndrome and control subjects. We found an imbalance in free radical scavengers in respiratory epithelial cells from children with Down syndrome, but this did not result in increased levels of either apoptosis or inflammation upon exposure to oxidative stress.
authors.affiliation: Emma Children's Hospital/Academic Medical Center, University of Amsterdam, Amsterdam.
authors.forename: Martijn
authors.initials: M
authors.lastname: Bruijn
authors.forename: René
authors.initials: R
authors.lastname: Lutter
authors.forename: Eric
authors.initials: E
authors.lastname: Eldering
authors.forename: Albert P
authors.initials: AP
authors.lastname: Bos
authors.forename: Job B M
authors.initials: JB
authors.lastname: van Woensel
mesh_terms: D000293:Adolescent; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004314:Down Syndrome / Q000378:metabolism* / Q000503:physiopathology*; D004848:Epithelium / Q000473:pathology*; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D008297:Male; D018384:Oxidative Stress; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology*; D012137:Respiratory System / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013481:Superoxides / Q000737:chemistry
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; C000606290:SOD1 protein, human; D013481:Superoxides; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1