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

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.