TY - JOUR
T1 - TNFα-stimulated protein 6 (TSG-6) reduces lung inflammation in an experimental model of bronchopulmonary dysplasia
AU - Bryan, Carleene
AU - Sammour, Ibrahim
AU - Guerra, Kasonya
AU - Sharma, Mayank
AU - Dapaah-Siakwan, Fredrick
AU - Huang, Jian
AU - Zambrano, Ronald
AU - Benny, Merline
AU - Wu, Shu
AU - Young, Karen
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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% O 2 ) 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.
AB - 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% O 2 ) 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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U2 - 10.1038/s41390-018-0250-2
DO - 10.1038/s41390-018-0250-2
M3 - Article
C2 - 30538263
AN - SCOPUS:85060172445
VL - 85
SP - 390
EP - 397
JO - Pediatric Research
JF - Pediatric Research
SN - 0031-3998
IS - 3
ER -