ArticleCellular and molecular gastroenterology and hepatology2022
C-Reactive Protein Protects Against Acetaminophen-Induced Liver Injury by Preventing Complement Overactivation.
Article in Cellular and molecular gastroenterology and hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- New Analogs of the Compstatin Family of Clinical Complement Inhibitors with Low Picomolar Target Affinity.Journal of medicinal chemistry · 2026Article
- Complement factor H supplementation rather than complete C3 knockout provides therapeutic benefits in IgA nephropathy.Molecular biomedicine · 2026Article
- Non-linear associations between inflammatory biomarkers andFrontiers in pediatrics · 2026Article
- Markers of inflammation and lung function in liver transplant recipients: results from a nationwide cohort study.Frontiers in immunology · 2026Article
- Review
- Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells.Cellular & molecular immunology · 2025Review
- Gentiopicroside improves DSS-induced ulcerative colitis and secondary liver injury in mice by enhancing the intestinal barrier and regulating the gut microbiome.Scientific reports · 2025Article
- Protection against prolonged pneumococcal infection involves structural changes in C-reactive protein and subsequent binding to both phosphocholine and amyloids on the bacterial surface.Frontiers in immunology · 2025Article
- C-reactive protein: structure, function, regulation, and role in clinical diseases.Frontiers in immunology · 2024Review
- Efficient expression and purification of rat CRP inFrontiers in immunology · 2024Article
- Monomeric C-reactive protein is associated with severity and prognosis of decompensated hepatitis B cirrhosis.Frontiers in immunology · 2024Article
- C-Reactive Protein Is Not the Driver Factor in Ulcerative Colitis.Gastroenterology research and practice · 2024Article
- The Potential Role of C-Reactive Protein in Metabolic-Dysfunction-Associated Fatty Liver Disease and Aging.Biomedicines · 2023Review
- Biomarkers of the Complement System Activation (C3a, C5a, sC5b-9) in Serum of Patients before and after Liver Transplantation.Biomedicines · 2023Article
- Regulation of the Innate Immune System as a Therapeutic Approach to Supporting Respiratory Function in ALS.Cells · 2023Article
- C-reactive protein deficiency ameliorates experimental abdominal aortic aneurysms.Frontiers in immunology · 2023Article
- Interorgan communication with the liver: novel mechanisms and therapeutic targets.Frontiers in immunology · 2023Review
- Macrophage-Targeted Sodium Chlorite (NP001) Slows Progression of Amyotrophic Lateral Sclerosis (ALS) through Regulation of Microbial Translocation.Biomedicines · 2022Article
- 3'mRNA sequencing reveals pro-regenerative properties of c5ar1 during resolution of murine acetaminophen-induced liver injury.NPJ Regenerative medicine · 2022Article
- C-Reactive Protein, a Promising Approach for Acetaminophen Hepatotoxicity.Cellular and molecular gastroenterology and hepatology · 2022Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsC-reactive protein (CRP) is a hepatocyte-produced marker of inflammation yet with undefined function in liver injury. We aimed to examine the role of CRP in acetaminophen-induced liver injury (AILI).
methodsThe effects of CRP in AILI were investigated using CRP knockout mice and rats combined with human CRP rescue. The mechanisms of CRP action were investigated in vitro and in mice with Fcγ receptor 2B knockout, C3 knockout, or hepatic expression of CRP mutants defective in complement interaction. The therapeutic potential of CRP was investigated by intraperitoneal administration at 2 or 6 hours post-AILI induction in wild-type mice.
resultsCRP knockout exacerbated AILI in mice and rats, which could be rescued by genetic knock-in, adeno-associated virus-mediated hepatic expression or direct administration of human CRP. Mechanistically, CRP does not act via its cellular receptor Fcγ receptor 2B to inhibit the early phase injury to hepatocytes induced by acetaminophen; instead, CRP acts via factor H to inhibit complement overactivation on already injured hepatocytes, thereby suppressing the late phase amplification of inflammation likely mediated by C3a-dependent actions of neutrophils. Importantly, CRP treatment effectively alleviated AILI with a significantly extended therapeutic time window than that of N-acetyl cysteine.
conclusionOur results thus identify CRP as a crucial checkpoint that limits destructive activation of complement in acute liver injury, and we argue that long-term suppression of CRP expression or function might increase the susceptibility to AILI.
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