2. Academic Validation
  3. C-reactive protein attenuates CCl4-induced acute liver injury by regulating complement system activation

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

  • Mol Immunol. 2025 Apr:180:44-54. doi: 10.1016/j.molimm.2025.02.008.
Zhao-Ming Tang 1,  Ping Yuan 2,  Ning Gao 3,  Jia-Geng Lei 2,  Mustafa Ahmed 1,  Yu-Xin Hua 2,  Ze-Rui Yang 1,  Qiu-Yu Li 4,  Hai-Yun Li 5
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Department of Nephrology, Nephrology & Critical Care Medicine of Xi'an International Science and Technology Cooperation Base, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
  • 2 MOE Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
  • 3 Department of Infectious Disease, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
  • 4 Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China. Electronic address: liqiuyu00@bjmu.edu.cn.
  • 5 School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Department of Nephrology, Nephrology & Critical Care Medicine of Xi'an International Science and Technology Cooperation Base, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.. Electronic address: lihaiy@xjtu.edu.cn.
PMID: 40010008 DOI: 10.1016/j.molimm.2025.02.008
Abstract

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 FcγR2b and early metabolic pathways. Instead, CRP suppresses the late-phase amplification of inflammation by inhibiting terminal complement pathway overactivation 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.

Keywords

Acute liver injury; C-reactive protein; Complement system; Inflammation.

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