Endothelial STING and STAT1 mediate IFN-independent effects of IL-6 in an endotoxemia-induced model of shock.

ABSTRACT: Severe systemic inflammatory reactions, including sepsis, often lead to shock, organ failure, and death, in part through an acute release of cytokines that promote vascular dysfunction. However, little is known about the vascular endothelial signaling pathways regulating the transcriptional profile in failing organs. Our work focused on signaling downstream of IL-6, due to its clinical importance as a biomarker for disease severity and predictor of mortality. Here, we show that loss of endothelial expression of the IL-6 pathway inhibitor SOCS3 promoted a type I IFN-like (IFNI-like) gene signature in response to endotoxemia in mouse kidneys and brains. In cultured primary human endothelial cells, IL-6 induced transient IFNI-like gene expression in a noncanonical, IFN-independent fashion. We

SUBMITTER: Martino N 

PROVIDER: S-EPMC12578408 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature