IRF-1 Intervention in the Classical ROS-Dependent Release of NETs during LPS-Induced Acute Lung Injury in Mice.
|
| Abstract |
Previously, we demonstrated that neutrophil extracellular traps (NETs) play an essential role in lipopolysaccharide (LPS)-induced acute lung injury. However, the underlying mechanism is unclear. In this study, we showed that knockout of interferon regulatory factor 1 (IRF-1) in mice strongly attenuated the generation of NETs and reactive oxygen species (ROS) production in neutrophils from bronchoalveolar lavage fluid and alleviated LPS-induced lung injury and systemic inflammation. Our in vitro experiments demonstrated that LPS-stimulated platelets induce NET release through two distinct processes: an ROS-independent early/rapid NETosis and a later ROS-dependent classical NETosis. Notably, the classical ROS-dependent pathway plays a dominant role in the generation of NETs. Furthermore, we showed that IRF-1 knockout does not affect the formation of NETs in early/rapid NETosis, but significantly attenuates ROS production and the generation of NETs in classical NETosis, which determines the total levels of NETs released by LPS-stimulated platelets. In conclusion, IRF-1 deficiency plays a key role in moderating the excessive NETs formed via ROS in the classical pathway and retaining the protective role of the low-NET levels generated in early/rapid NETosis, which may serve as a novel target in acute lung injury/acute respiratory distress syndrome.
|
|---|---|
| Authors | Shuai Liu, Yinyan Yue, Pinhua Pan, Lemeng Zhang, Xiaoli Su, Haitao Li, Haosi Li, Yi Li, Minhui Dai, Qian Li, Zhi Mao |
| Journal | Inflammation (Inflammation) Vol. 42 Issue 1 Pg. 387-403 (Feb 2019) ISSN: 1573-2576 [Electronic] United States |
| PMID | 30315525 (Publication Type: Journal Article) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!