TNFα-stimulated protein 6 (TSG-6) reduces lung inflammation in an experimental model of bronchopulmonary dysplasia

Carleene Bryan, Ibrahim Sammour, Kasonya Guerra, Mayank Sharma, Fredrick Dapaah-Siakwan, Jian Huang, Ronald Zambrano, Merline Benny, Shu Wu, Karen Young

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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% 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.

Original languageEnglish (US)
Pages (from-to)390-397
Number of pages8
JournalPediatric Research
Volume85
Issue number3
DOIs
StatePublished - Feb 1 2019

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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