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

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.

Phosphocholine-Modified Lipooligosaccharides of Haemophilus influenzae Inhibit ATP-Induced IL-1β Release by Pulmonary Epithelial Cells

“…We used A549 cells resembling alveolar epithelial cells type II [ 27 , 28 ], and the bronchial epithelial cell line Calu-3 [ 29 ] to ascertain the purity of the epithelial cells. The capacity A549 cells to form NLRP3 inflammasomes and to secrete mature IL-1β has been shown before [ 54 , 55 ] and we demonstrate in this study that Calu-3 cells are also able to secrete IL-1β. These data must be interpreted with caution, because cell lines never fully reflect the properties of primary cells.…”

Procyanidin B2 inhibits lipopolysaccharide‑induced apoptosis by suppressing the Bcl‑2/Bax and NF‑κB signalling pathways in human umbilical vein endothelial cells

“…By contrast, Bax, a proapoptotic protein, transfers from the cytosol to the mitochondria to promote Cyt-c release from mitochondria, resulting in apoptosis induction and DNA damage (8). Previous studies have demonstrated that apoptosis induction by stimuli is associated with the Bcl-2/Bax signalling pathway, and perfluorocarbon decreased blast injury-induced cell damage by inhibiting the Bcl-2/Bax, NF-κB and MAPK signalling pathways in A549 cells (9)(10)(11)(12)(13). The caspase family are apoptosis-specific targets, and as cysteine-aspartic acid proteases, caspase-3 and caspase-7 directly induce apoptosis after sequential activation (14).…”

Quantitative proteomic analysis and identification of differentially expressed proteins involved in blast exposure-induced inflammatory response

“…Moreover, the administration of decay accelerating factor effectively inhibited the in ammatory response by regulating the complement system [29]. Another study by Zhang et al found that blast exposure obviously reduced cell adhesion abilities of A549 cells in vitro, and induced in ammatory response, apoptosis and oxidative damage [30]. Per uorocarbon administration signi cantly inhibited blast-induced in ammation through NF-κB and MAPK signaling pathways.…”