Expression of STING Is Increased in Monocyte-derived Macrophages and Contributes to Liver Inflammation in Hepatic Ischemia-Reperfusion Injury

Ischemia/reperfusion (I/R) injury, aggravated by innate immune cell-mediated inflammatory response, is a major problem in liver transplantation. Stimulator of interferon gene (STING) is a crucial regulatory signal molecule in the DNA-sensing pathway, and its activation can produce strong innate immunity. However, the STING-mediated innate immune pathway in hepatic I/R injury has not been fully elucidated. In this study, we first examined the STING expression changes in the liver tissues of mice after hepatic I/R injury by using quantitative polymerase chain reaction and Western blot assays. We then investigated the role of STING in I/R injury by using a murine hepatic I/R model. STING up-regulation in mouse liver tissues in response to I/R injury and STING deficiency in myeloid cells was found to significantly ameliorate I/R-induced liver injury and inflammatory responses. The use of STING inhibitors in hepatic I/R injury has also displayed a satisfactory outcome. Mechanically, inhibition of hypoxia-inducible factor-1 alpha and enhancement of phosphorylated amp-activated protein kinase to reduce macrophage activation may be its protective effect on hepatic I/R injury. These findings show the potential regulatory effects of STING in hepatic I/R and provide a new method for clinical protection of hepatic I/R injury.