Neutrophils undergo switch of apoptosis to NETosis during murine fatty liver injury via S1P receptor 2 signaling

• DOI: 10.1038/s41419-020-2582-1
• Publication Date: 2020-05-18T13:08:02Z
• Authors: Xinhao Zhao; Le Yang; Na Chang; Lei Hou; Xuan Zhou; Lin Yang; Liying Li
• Keywords: Neutrophil Extracellular Traps; Sphingosine Kinase; Steatohepatitis

Abstract Inappropriate neutrophil infiltration and subsequent extracellular trap (NET) formation have been confirmed to be involved in chronic inflammatory conditions. Fatty liver disease is an increasingly severe health problem worldwide currently considered the most common cause of disease. Sphingosine 1-phosphate (S1P), a product membrane sphingolipid metabolism, regulates vital physiological pathological actions by inducing activation various cell types through S1P receptors (S1PRs). Here, we seek determine S1PR-mediated effects on during inflammation. In this study, NETs are detected early stage methionine-choline-deficient high-fat (MCDHF) diet-induced injury. NET depletion deoxyribonuclease I intraperitoneal injection significantly protects from MCDHF-induced injury vivo. Meanwhile, show that levels myeloperoxidase-DNA complex (NET marker) serum present positive correlation with sphingosine kinase1 (S1P rate-limiting enzyme) messenger RNA expression or injured MCDHF-fed mice. vitro, S1PR 2 participates redirection apoptosis NETosis via Gα i/o , signal-regulated kinase, p38 mitogen-activated protein reactive oxygen species signaling pathways. Moreover, knockdown mice -siRNA intravenous inhibits damaged tissue then alleviates hepatic inflammation fibrosis. Conclusion: fatty disease, -mediated plays important role evolvement