Human β-Defensin-2 Improves Hyperoxia-Induced Lung Structural and Functional Injury in Neonatal Rats

Abstract

Background Bronchopulmonary dysplasia (BPD) is a major complication of extreme prematurity, characterized by alveolar simplification and pulmonary malfunction. Hyperoxia-induced lung injury in neonatal rats has been used as a model of BPD, as indicated by lung architectural change and alveolar simplification that resembles clinical feature of BPD. β-defensin-2 (BD2) plays an important role in lung diseases by inhibiting inflammation response. However, little is known about its role in BPD. The aim of this study was to determine the effect of human BD2 (hBD2) gene on hyperoxia-induced animal model of BPD. Material/Methods The neonatal rats were exposed to 90% oxygen (O 2 ) continuously for 14 days to mimic the BPD-like lung injury. These rats were then randomly assigned to the following four groups: in room air (air), in 90% O 2 , in 90% O 2 with null adenovirus vector infection (O 2 +Ad), and in 90% O 2 with gene therapy through adenovirus transfected hBD2 (O 2 +Ad-hBD2). Morphology of lungs, pulmonary function and expression of inflammatory cytokines on P7, P10, P14, and P21 were documented and compared across the 4 groups. Results The overexpression of hBD2 mediated by the adenovirus vector was successfully constructed. hBD2 gene therapy increased hBD2 mRNA expression, increased radial alveolar count (RAC), lung volume and compliance, decreased mean linear intercept (MLI), tissue damping, and elastance. Furthermore, pro-inflammatory cytokines IL-1β, IL-6, and TNF-α were inhibited and anti-inflammatory cytokines IL-10 was increased in the lungs of rats in O 2 +Ad-hBD2 group. Conclusions In hyperoxia-induced rat models of BPD, hBD2 promotes alveolarization and improves pulmonary function. The mechanism may contribute in alleviating inflammation response and inhibiting pro-inflammatory factors including IL-1β, IL-6, and TNF-α.

Tetrandrine attenuates hyperoxia-induced lung injury in newborn rats via NF-κB p65 and ERK1/2 pathway inhibition

“…Hyperoxia-induced lung injury in newborn rats has long been used as a model of BPD (5,24). Previous studies have observed lung function to be remarkably impaired in hyperoxia-induced BPD with an abnormal increase in airway resistance and a decrease in dynamic lung compliance (25,26). In the present study, decreased lung function was also observed in newborn rats under hyperoxia exposure.…”

Sheep β-Defensin 2 Regulates Escherichia coli F17 Resistance via NF-κB and MAPK Signaling Pathways in Ovine Intestinal Epithelial Cells

“…Recently, scholars in various fields tend to use gene overexpression technology to explore the mechanism of β-defensin regulating cancer diseases, species including human [ 25 , 26 ], pig [ 27 , 28 ], mice [ 29 , 30 ], etc. Similarly, RNAi technology is also increasingly used in gene functional analysis [ 31 ].…”

Effects of celecoxib on AQP-1, NF-κB and apoptosis in lung tissue of neonatal rats with hyperoxia-induced lung injury

“…This may be due to the fact that hyperoxia can lead to excessive accumulation of reactive oxygen species in the body, promote the inflammatory factors expression, such as TNF-α, IL-1 hormone and IL-6 in the lung, and activate related pathways. Celecoxib can significantly inhibit pulmonary inflammatory factors expression (10).…”