Perfluorocarbon reduces cell damage from blast injury by inhibiting signal paths of NF-κB, MAPK and Bcl-2/Bax signaling pathway in A549 cells.

Zhaorui Zhang,Lu Cao,Huaidong Li,Zhixin Liang,Wenjie Wang,Liangan Chen,Chunsun Li,Changlin Liu,Yanqin Li,Danyang She,Zhen Yang,Yi-Hsien Hsieh

doi:10.1371/journal.pone.0173884

Zhaorui Zhang, Lu Cao + Show 10 more

Open Access

https://doi.org/10.1371/journal.pone.0173884

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Abstract

Background and objectiveBlast lung injury is a common type of blast injury and has very high mortality. Therefore, research to identify medical therapies for blast injury is important.Perfluorocarbon (PFC) is used to improve gas exchange in diseased lungs and has anti-inflammatory functions in vitro and in vivo. The aim of this study was to determine whether PFC reduces damage to A549 cells caused by blast injury and to elucidate its possible mechanisms of action.Study design and methodsA549 alveolar epithelial cells exposed to blast waves were treated with and without PFC. Morphological changes and apoptosis of A549 cells were recorded. PCR and enzyme-linked immunosorbent assay (ELISA) were used to measure the mRNA or protein levels of IL-1β, IL-6 and TNF-α. Malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity levels were detected. Western blot was used to quantify the expression of NF-κB, Bax, Bcl-2, cleaved caspase-3 and MAPK cell signaling proteins.ResultsA549 cells exposed to blast wave shrank, with less cell-cell contact. The morphological change of A549 cells exposed to blast waves were alleviated by PFC. PFC significantly inhibited the apoptosis of A549 cells exposed to blast waves. IL-1β, IL-6 and TNF-α cytokine and mRNA expression levels were significantly inhibited by PFC. PFC significantly increased MDA levels and decreased SOD activity levels. Further studies indicated that NF-κB, Bax, caspase-3, phospho-p38, phosphor-ERK and phosphor-JNK proteins were also suppressed by PFC. The quantity of Bcl-2 protein was increased by PFC.ConclusionOur research showed that PFC reduced A549 cell damage caused by blast injury. The potential mechanism may be associated with the following signaling pathways:1) the signaling pathways of NF-κB and MAPK, which inhibit inflammation and reactive oxygen species (ROS); and 2) the signaling pathways of Bcl-2/Bax and caspase-3, which inhibit apoptosis.

Highlights

The morbidity and mortality of blast injury are increasing, both on the battleground and in daily life [1]
A549 cells exposed to blast wave shrank, with less cell-cell contact
PFC significantly inhibited the apoptosis of A549 cells exposed to blast waves

Summary

Introduction

The morbidity and mortality of blast injury are increasing, both on the battleground and in daily life [1]. A primary blast injury is the direct result of a blast wave. A secondary blast injury is caused by flying debris. A tertiary blast injury is caused by moving bodies and debris pushed by the blast wave. The air-containing organs, such as the lungs, are at an increased risk of primary blast injury [5,6]. There are no effective medical therapies for blast lung injury, medical scientists have tested many methods, such as mechanical ventilation, fluid resuscitation and hyperbaric oxygen [10]. The aim of this study was to determine whether PFC reduces damage to A549 cells caused by blast injury and to elucidate its possible mechanisms of action

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