biostudies-literatureUnknown6(2)Xiong YHepatic ischemia-reperfusion (I/R) injury frequently occurs during the perioperative phase of liver surgery. Inappropriate activation of STING signaling can trigger excessive inflammation response to aggravate hepatic I/R injury. Dimethyl fumarate (DMF) is an FDA-approved immunomodulatory drug used to treat multiple sclerosis and psoriasis due to its notable anti-inflammation properties. However, the mechanism and targets of DMF in immunomodulation remain unclear. Here, we found that DMF suppresses cGAS-STING activation induced by HSV-1, hering testis DNA, and mitochondrial DNA in a variety of cells. DMF significantly reduces hepatic I/R injury and inhibits cGAS-STING pathway activation in mice. The alleviating effect of DMF on hepatic I/R injury was negligible in STING-knockout mice. MechMedComme70077https://www.ebi.ac.uk/biostudies/studies/S-EPMC11773390biostudies-literatureDimethyl fumarate alleviate hepatic ischemia-reperfusion injury through suppressing cGAS-STING signaling.PMC11773390Xiong YQiu XLiang WChen JQiu DQin YLi KZhang BSong JfalseDimethyl fumarate alleviate hepatic ischemia-reperfusion injury through suppressing cGAS-STING signaling.Hepatic ischemia-reperfusion (I/R) injury frequently occurs during the perioperative phase of liver surgery. Inappropriate activation of STING signaling can trigger excessive inflammation response to aggravate hepatic I/R injury. Dimethyl fumarate (DMF) is an FDA-approved immunomodulatory drug used to treat multiple sclerosis and psoriasis due to its notable anti-inflammation properties. However, the mechanism and targets of DMF in immunomodulation remain unclear. Here, we found that DMF suppresses cGAS-STING activation induced by HSV-1, hering testis DNA, and mitochondrial DNA in a variety of cells. DMF significantly reduces hepatic I/R injury and inhibits cGAS-STING pathway activation in mice. The alleviating effect of DMF on hepatic I/R injury was negligible in STING-knockout mice. Mech2025-01-01T00:00:00Z2025 Feb2025-04-04T20:56:44.76Z2025-04-04T20:56:44.76ZS-EPMC117733903987728610.1002/mco2.70077