Constitutive Androstane Receptor in Macrophages Regulates Toll-Like Receptor 4-Mediated Innate Immune Responses Against Endotoxemic Liver Injury.

ABSTRACT: Macrophage proinflammatory hyperactivation drives the pathogenesis of acute liver injury, a common complication of sepsis. The role of the nuclear receptor constitutive androstane receptor (CAR) in endotoxin-induced liver injury remains unclear. Here, this study reports that CAR is highly expressed in human and murine macrophages. CAR activation markedly attenuated endotoxin-induced liver damage, alleviating hepatocyte death and hepatic inflammation. Macrophage-hepatocyte coculture confirmed that CAR inhibited inflammation through macrophage crosstalk. CAR-mediated hepatoprotection and anti-inflammatory effects are absent in AAV8-F4/80-shCar-treated mice, confirming the essential role of CAR in macrophages. Mechanistically, CAR is found to interact with Tlr4, and the suppressive effects of

SUBMITTER: Cao R 

PROVIDER: S-EPMC12622418 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature