Attenuation of Hyperoxic Lung Injury in Newborn Thioredoxin-1-Overexpressing Mice through the Suppression of Proinflammatory Cytokine mRNA Expression.

Nobuhiko Nagano,Fumihiko Namba,Kohei Osada,Junichi Ozawa,Takaaki Watanabe,Masanori Tamura,Fuyu Miyake,Kikumi Matsuoka,Kosuke Tanaka,Shun Matsumura

doi:10.3390/biomedicines8030066

Nobuhiko Nagano, Fumihiko Namba + Show 8 more

Open Access

https://doi.org/10.3390/biomedicines8030066

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Abstract

The role of thioredoxin-1 (TRX), a small redox-active protein with antioxidant effects, during hyperoxic lung injury in newborns remains undetermined. We investigated TRX impact on hyperoxic lung injury in newborn TRX transgenic (TRX-Tg) and wildtype (WT) mice exposed to 21% or 95% O2 for four days, after which some mice were allowed to recover in room air for up to 14 days. Lung morphology was assessed by hematoxylin/eosin and elastin staining, as well as immunostaining for macrophages. The gene expression levels of proinflammatory cytokines were evaluated using quantitative real-time polymerase chain reaction. During recovery from hyperoxia, TRX-Tg mice exhibited an improved mean linear intercept length and increased number of secondary septa in lungs compared with the WT mice. Neonatal hyperoxia enhanced the mRNA expression levels of proinflammatory cytokines in the lungs of both TRX-Tg and WT mice. However, interleukin-6, monocyte chemoattractant protein-1, and chemokine (C-X-C motif) ligand 2 mRNA expression levels were reduced in the lungs of TRX-Tg mice compared with the WT mice during recovery from hyperoxia. Furthermore, TRX-Tg mice exhibited reduced macrophage infiltration in lungs during recovery. These results suggest that in newborn mice TRX ameliorates hyperoxic lung injury during recovery likely through the suppression of proinflammatory cytokines.

Highlights

Bronchopulmonary dysplasia (BPD) is one of the most severe complications affecting premature infants [1]
The effect of neonatal hyperoxia on body weight was assessed in the WT and TRX transgenic (TRX-Tg) mice
On day 4 after neonatal hyperoxia, no significant decrease in body weight was observed in the WT or the TRX-Tg mice compared with their normoxic counterparts

Summary

Introduction

Bronchopulmonary dysplasia (BPD) is one of the most severe complications affecting premature infants [1]. Recent studies have investigated the long-term consequences of BPD on the respiratory health of older children and adults. In extremely low-birth-weight survivors, who were born weighing less than 1000 g, lung function values at 8 and 12 years of age were lower than the reference values, especially in children with a history of severe BPD and in those exhibiting. Several alternative therapies using drugs such as inhaled nitric oxide and vitamin A have failed to consistently produce effective clinical outcomes, and most current therapies continue to be supportive [4,5]. Current studies are evaluating multiple therapies including caffeine, furosemide, systemic and inhaled corticosteroids, inositol, and cell therapy to characterize their efficacy and safety profiles [6]

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