C-reactive protein attenuates CCl4-induced acute liver injury by regulating complement system activation

Acute liver injury is liver dysfunction caused by multiple factors without any pre-existing liver disease. C-reactive protein (CRP) is an acute-phase protein produced by hepatocytes, serving as a marker of inflammation and tissue damage. However, its role in CCl4-induced acute liver injury has not been elucidated. Here, we report that CRP protects against CCl4-induced acute liver injury by regulating complement activation. CRP knockout exacerbates CCl4-induced acute liver injury in mice and rats, markedly enhances tissue damage, and reduces survival. Administration of exogenous CRP to CRP-knockout mice rescues the CCl4-induced liver injury phenotype. The protective effect of CRP is independent of its cellular receptor Fc gamma R2b and early metabolic pathways. Instead, CRP suppresses the late-phase amplification of inflammation by inhibiting terminal complement pathway over- activation in injured hepatocytes via factor H recruitment. In complement C3 knockout (C3-/-) mice, the protective effect of CRP against CCl4-induced acute liver injury is lost. These results suggest that CRP can alleviate CCl4-induced acute liver injury by regulating the complement pathway, providing a theoretical basis for CRP's potential involvement and regulation of disease severity.