Research Paper Volume 13, Issue 24 pp 26148—26160
Free fatty acids-induced neutrophil extracellular traps lead to dendritic cells activation and T cell differentiation in acute lung injury
- 1 Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- 2 Institute of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China
- 3 Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Received: May 4, 2021 Accepted: November 22, 2021 Published: December 27, 2021
https://doi.org/10.18632/aging.203802How to Cite
Copyright: © 2021 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.