Abstract
This study aimed to investigate whether free fatty acids (FFAs) could induce the release of neutrophil extracellular traps (NETs), as well as the mechanism of FFAs-induced NETs in acute lung injury (ALI). FFAs were used to induce NETs production. The reactive oxygen species (ROS) production was detected after FFA and NADPH oxidase inhibitor treatments. The association between FFAs-induced NETs and the activation of p38, ERK, and JNK pathways was investigated. The effect of FFAs-induced NETs on the dendritic cells (DCs) activation and T cell differentiation was investigated. FFAs could induce neutrophils to produce NETs. FFAs significantly promoted ROS production and increased the expression of ERK, p38 and JNK, and treatment of the inhibitors of NAPDH oxidase (DPI), p38 (SB202190), ERK1/2 (U0126) and JNK (SP600125) inhibited FAAs-induced NETs production. FFAs induced NETs could promote DCs activation and consequently led to the differentiation of primary CD4+ T cells into Th1 and Th17 cells and the release of IL-1β, IL-12 and TNF-α. FFAs are capable of inducing NETs via NOX, ERK, p38 and JNK pathways. FFA-induced NETs further lead to DCs activation and T cell differentiation, which can well explain the mechanism of ALI caused by FFAs.
Highlights
Acute lung injury (ALI) is a critical illness syndrome characterized by excessive uncontrolled inflammation and apoptosis [1]
The present study evaluated the mechanism of FFAsinduced neutrophil extracellular traps (NETs) in acute lung injury (ALI) in vitro
We found that free fatty acids (FFAs) could induce neutrophils to produce NETs
Summary
Acute lung injury (ALI) is a critical illness syndrome characterized by excessive uncontrolled inflammation and apoptosis [1]. As the most severe form of ALI, acute respiratory distress syndrome (ARDS) is an acute and progressive diffuse inflammatory lung injury caused by various intrapulmonary or extrapulmonary factors. The clinical manifestations of ARDS are respiratory distress and refractory hypoxemia [2]. ARDS patients account for 10% of intensive care unit (ICU) patients, and its mortality rate is up to 35–46% [3]. Due to lack of accepted diagnostic test, ALI/ARDS remains a challenging entity for clinical investigation. Elucidation of key mechanism underlying lung injury will have great significance in improving clinical outcomes
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