Aging aggravated liver ischemia and reperfusion injury by promoting STING-mediated NLRP3 activation in macrophages.

ABSTRACT: Although aggravated liver injury has been reported in aged livers post-ischemia and reperfusion (IR), the underlying mechanism of innate immune activation of aged macrophages is not well understood. Here, we investigated whether and how Stimulator of interferon genes (STING) signaling regulated macrophage proinflammatory activation and liver IR injury. Mice were subjected to hepatic IR in vivo. Macrophages isolated from IR-stressed livers and bone marrow-derived macrophages (BMDMs) from young and aged mice were used for in vitro studies. Enhanced nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3) activation was found in both livers and macrophages of aged mice post-IR. NLRP3 knockdown in macrophages inhibited intrahepatic inflammation and liver injury in both yo

SUBMITTER: Zhong W 

PROVIDER: S-EPMC7431827 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature