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


METHODS
A549 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.


RESULTS
A549 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.


CONCLUSIONS
Our 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.
Department of Respiration, Chinese PLA General Hospital, Beijing City, People's Republic of China.
Zhaorui
Z
Zhang
Department of Respiration, Chinese PLA General Hospital, Beijing City, People's Republic of China.
Zhixin
Z
Liang
Department of Respiratory Disease, The 88th Hospital of Chinese PLA, Tai'an City, Shandong Province, People's Republic of China.
Huaidong
H
Li
Department of Respiration, Chinese PLA General Hospital, Beijing City, People's Republic of China.
Chunsun
C
Li
Department of Respiration, Chinese PLA General Hospital, Beijing City, People's Republic of China.
Zhen
Z
Yang
Department of Respiration, Chinese PLA General Hospital, Beijing City, People's Republic of China.
Yanqin
Y
Li
Department of Respiration, Chinese PLA General Hospital, Beijing City, People's Republic of China.
Danyang
D
She
Department of Respiration, Chinese PLA General Hospital, Beijing City, People's Republic of China.
Lu
L
Cao
Department of State Key Laboratory of Explosion Science and Technology, The Beijing University of Technology, Beijing City, People's Republic of China.
Wenjie
W
Wang
Department of State Key Laboratory of Explosion Science and Technology, The Beijing University of Technology, Beijing City, People's Republic of China.
Changlin
C
Liu
Department of Respiration, Chinese PLA General Hospital, Beijing City, People's Republic of China.
Liangan
L
Chen
D000072283:A549 Cells; D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D001753:Blast Injuries / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D005466:Fluorocarbons / Q000494:pharmacology*; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494826:BAX protein, human; D005466:Fluorocarbons; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; D053148:Caspase 3