Knockdown of EDA2R alleviates hyperoxia-induced lung epithelial cell injury by inhibiting NF-κB pathway

Main Article Content

Nan Jia
Yi Jia
Fen Yang
Wenchao Du

Keywords

bronchopulmonary dysplasia, EDA2R, hyperoxia, inflammation, lung epithelial cells, NF-κB pathway, oxidative stress

Abstract

Background: Long-term hyperoxia impairs growth of the lungs and contributes to development of bronchopulmonary dysplasia. Ectodysplasin A (EDA) binds to ectodysplasin A2 receptor (EDA2R) and is essential for normal prenatal development. The functioning of EDA2R in bronchopulmonary dysplasia is investigated in this study.


Methods: Murine lung epithelial cells (MLE-12) were exposed to hyperoxia to induce cell injury. Cell viability and apoptosis were detected, respectively, by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay and flow cytometry. Inflammation and oxidative stress were evaluated by enzyme-linked immunosorbent serologic assay.


Results: Hyperoxia decreased cell viability and promoted cell apoptosis of MLE-12. EDA2R was elevated in hyperoxia-induced MLE-12. Silencing of EDA2R enhanced cell viability and reduced cell apoptosis of hyperoxia-induced MLE-12. Hyperoxia-induced up-regulation of tumor necrosis factor alpha (TNF-α), Interleukin (IL)-1β, and IL-18 as well as MLE-12 was suppressed by knockdown of EDA2R. Inhibition of EDA2R down-regulated the level of malondialdehyde (MDA), up-regulated superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) in hyperoxia-induced MLE-12. Interference of EDA2R attenuated hyperoxia-induced increase in p-p65 in MLE-12.


Conclusion: Knockdown of EDA2R exerted anti-inflammatory and antioxidant effects against hyperoxia-induced injury in lung epithelial cells through inhibition of nuclear factor kappa B (NF-κB) pathway.

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