Fig. 6. Diagram of how STING inhibitor alleviated endotoxin-induced acute lung injury.

LPS inhalation leads to the activation of vascular endothelial cells. Once activated, vascular endothelial cells secrete the chemokines (such as Ccl2, Ccl5, Ccl20, and Cxcl10) and recruit neutrophils and macrophages, resulting in the massive production of inflammatory cytokines and further inflammatory positive feedback loop. STING inhibitor attenuates vascular endothelium activation, prevents vascular endothelial cells–mediated immune cells chemotaxis and adhesion, and inhibits the macrophages and neutrophils infiltration, and relieves inflammation. Mechanistically, STING inhibition downregulates the phosphorylation of transcription factor STAT1, which subsequently influences the binding of chemokine and adhesive molecule gene promoter.