Abstract
Background
Inflammation is a key factor in the pathogenesis of bronchopulmonary dysplasia (BPD). Tumor necrosis factor–stimulated protein 6 (TSG-6) is a glycoprotein that modulates inflammation. Here we tested the hypothesis that intra-tracheal (IT) administration of an adenovirus overexpressing TSG-6 (AdTSG-6) would decrease inflammation and restore lung structure in experimental BPD.
Methods
Newborn Sprague-Dawley rats exposed to normoxia (RA) or hyperoxia (85% O2) from postnatal day (P) 1–P14 were randomly assigned to receive IT AdTSG-6 or placebo (PL) on P3. The effect of IT AdTSG-6 on lung inflammation, alveolarization, angiogenesis, apoptosis, pulmonary vascular remodeling, and pulmonary hypertension were evaluated on P14. Data were analyzed by two-way ANOVA.
Results
TSG-6 mRNA was significantly increased in pups who received IT AdTSG-6. Compared to RA, hyperoxia PL-treated pups had increased NF-kβ activation and lung inflammation. In contrast, IT AdTSG-6 hyperoxia-treated pups had decreased lung phosphorylated NF-kβ expression and markers of inflammation. This was accompanied by an improvement in alveolarization, angiogenesis, pulmonary vascular remodeling, and pulmonary hypertension.
Conclusions
IT AdTSG-6 decreases lung inflammation and improves lung structure in neonatal rats with experimental BPD. These findings suggest that therapies that increase lung TSG-6 expression may have beneficial effects in preterm infants with BPD.
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Bryan, C., Sammour, I., Guerra, K. et al. TNFα-stimulated protein 6 (TSG-6) reduces lung inflammation in an experimental model of bronchopulmonary dysplasia. Pediatr Res 85, 390–397 (2019). https://doi.org/10.1038/s41390-018-0250-2
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DOI: https://doi.org/10.1038/s41390-018-0250-2
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