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 journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
JournalPediatric Research
DOIs
StateAccepted/In press - Jan 1 2018

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Bronchopulmonary Dysplasia
Adenoviridae
Pneumonia
Theoretical Models
Hyperoxia
Lung
Proteins
Inflammation
Pulmonary Hypertension
Placebos
Premature Infants
Sprague Dawley Rats
Glycoproteins
Analysis of Variance
Necrosis
Apoptosis
Messenger RNA
Neoplasms

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

TNFα-stimulated protein 6 (TSG-6) reduces lung inflammation in an experimental model of bronchopulmonary dysplasia. / Bryan, Carleene; Sammour, Ibrahim; Guerra, Kasonya; Sharma, Mayank; Dapaah-Siakwan, Fredrick; Huang, Jian; Zambrano, Ronald; Benny, Merline; Wu, Shu; Young, Karen.

In: Pediatric Research, 01.01.2018.

Research output: Contribution to journalArticle

Bryan, Carleene ; Sammour, Ibrahim ; Guerra, Kasonya ; Sharma, Mayank ; Dapaah-Siakwan, Fredrick ; Huang, Jian ; Zambrano, Ronald ; Benny, Merline ; Wu, Shu ; Young, Karen. / TNFα-stimulated protein 6 (TSG-6) reduces lung inflammation in an experimental model of bronchopulmonary dysplasia. In: Pediatric Research. 2018.
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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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AU - Sammour, Ibrahim

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AU - Dapaah-Siakwan, Fredrick

AU - Huang, Jian

AU - Zambrano, Ronald

AU - Benny, Merline

AU - Wu, Shu

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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% 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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