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Published on: December 11, 2020
Effect of oxidative stress on respiratory epithelium from children with Down syndrome
Martijn Bruijn1, René Lutter, Eric Eldering
1Emma Children's Hospital/Academic Medical Center, University of Amsterdam, Amsterdam.
Insights
Children with Down syndrome show an imbalance in free radical scavengers in respiratory cells. However, this imbalance did not lead to increased apoptosis or inflammation when exposed to oxidative stress.
Area of Science:
- Cellular Biology
- Immunology
- Genetics
Background:
- Children with Down syndrome have an elevated risk for acute respiratory distress syndrome.
- Abnormal regulation of inflammation and apoptosis in Down syndrome contributes to acute respiratory distress syndrome pathophysiology.
- An imbalance in free radical scavengers is implicated in these abnormalities.
Purpose of the Study:
- To investigate the expression of free radical scavengers in respiratory epithelial cells of children with Down syndrome.
- To determine the effect of oxidative stress on apoptosis and inflammation in these cells.
Main Methods:
- Primary nasal epithelial cells were cultured from children with Down syndrome (n=12) and controls (n=17).
- Cells were exposed to oxidative stress by supplementing with superoxide.
- Expression of free radical scavengers and levels of inflammatory markers were analyzed.
Main Results:
- CuZn-superoxide dismutase expression was 28% higher (p=0.06) in Down syndrome cells.
- Catalase was 36% lower (p=0.04) and glutathione peroxidase was 73% lower (p=0.004) in Down syndrome cells.
- No significant differences in apoptosis or inflammatory markers (IL-1β, IL-6, IL-8, VEGF, G-CSF) were observed after oxidative stress exposure.
Conclusions:
- Respiratory epithelial cells from children with Down syndrome exhibit an imbalance in free radical scavengers.
- This imbalance does not appear to increase susceptibility to apoptosis or inflammation under oxidative stress conditions.
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.
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