| First Author | Liu S | Year | 2019 |
| Journal | Inflammation | Volume | 42 |
| Issue | 1 | Pages | 387-403 |
| PubMed ID | 30315525 | Mgi Jnum | J:313194 |
| Mgi Id | MGI:6791574 | Doi | 10.1007/s10753-018-0903-7 |
| Citation | Liu S, et al. (2019) IRF-1 Intervention in the Classical ROS-Dependent Release of NETs during LPS-Induced Acute Lung Injury in Mice. Inflammation 42(1):387-403 |
| abstractText | 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. |
