ArticleCellular & molecular immunology2015
Over-activation of TLR5 signaling by high-dose flagellin induces liver injury in mice.
Article in Cellular & molecular immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 73 citations in OpenAlex.
- Liver Injury and Endotoxemia in Male and Female Alcohol-Dependent Individuals Admitted to an Alcohol Treatment Program.Alcoholism, clinical and experimental research · 2017Trial
- Gut microbiota shaping fatty liver disease progression.Life science alliance · 2027Review
- Inflammatory gut-liver crosstalk: mechanisms and therapeutic targets.Experimental & molecular medicine · 2026Review
- The gut-liver axis in drug-induced liver injury (DILI): Interplay between gut microbiota, intestinal barrier, and immune system.Acta pharmaceutica Sinica. B · 2026Review
- Gut-liver axis molecular mechanisms in alcohol-associated liver disease.Alcohol (Fayetteville, N.Y.) · 2026Review
- Pre-diagnostic immunological markers of bacterial translocation and liver cancer risk: A nested case-control analysis of 12 prospective cohorts.International journal of cancer · 2026Article
- Neutrophil extracellular traps in diabetic wound healing: mechanisms, pathological roles, and therapeutic implications.Burns & trauma · 2026Review
- Mechanisms of hepatocellular carcinoma and cirrhosis development in concurrent steatotic liver disease and chronic hepatitis B.Clinical and molecular hepatology · 2025Review
- Structural engineering of flagellin as vaccine adjuvant: quest for the minimal domain of flagellin for TLR5 activation.Molecular biology reports · 2025Review
- Review
- Nano biomaterials based strategies for enhanced brain targeting in the treatment of neurodegenerative diseases: an up-to-date perspective.Journal of nanobiotechnology · 2023Review
- A Bacterial mRNA-Lysis-Mediated Cargo Release Vaccine System for Regulated Cytosolic Surveillance and Optimized Antigen Delivery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Biomarkers of gut barrier dysfunction and risk of hepatocellular carcinoma in the REVEAL-HBV and REVEAL-HCV cohort studies.International journal of cancer · 2023Article
- Effect of sweet potato purple acid phosphatase on Pseudomonas aeruginosa flagellin-mediated inflammatory response in A549 cells.Animal bioscience · 2023Article
- A candidate glycoconjugate vaccine induces protective antibodies in the serum and intestinal secretions, antibody recall response and memory T cells and protects against both typhoidal and non-typhoidalFrontiers in immunology · 2023Article
- Flagellin/Virus-like Particle Hybrid Platform with High Immunogenicity, Safety, and Versatility for Vaccine Development.ACS applied materials & interfaces · 2022Article
- Bacterial Translocation in Gastrointestinal Cancers and Cancer Treatment.Biomedicines · 2022Review
- STING signaling activation inhibits HBV replication and attenuates the severity of liver injury and HBV-induced fibrosis.Cellular & molecular immunology · 2022Article
- Nanogels as Novel Nanocarrier Systems for Efficient Delivery of CNS Therapeutics.Frontiers in bioengineering and biotechnology · 2022Review
- MicroRNA-5112 Targets IKKγ to Dampen the Inflammatory Response and Improve Clinical Symptoms in Both Bacterial Infection and DSS-Induced Colitis.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Flagellin is a potent activator of a broad range of cell types that are involved in innate and adaptive immunity. Therefore, it is a good adjuvant candidate for vaccines, and it might function as a biological protectant against both major acute radiation syndrome during cancer radiotherapy and a mitigator of radiation emergencies. However, accumulating evidence has implicated flagellin in the occurrence of some inflammatory diseases, such as acute lung inflammation, cardiovascular collapse and inflammatory bowel disease. The aim of this study was to elucidate whether only flagellin-TLR5 signaling activation plays a role in the pathophysiology of liver or whether some other flagellin activity also contributes to liver injury either via bacterial infections or during clinical applications. Recombinant flagellin proteins with or without TLR5-stimulating activity were used to evaluate the role of flagellin-TLR5 signaling in liver injury in wild-type and TLR5 KO mice. Gross lesions and large areas of hepatocellular necrosis were observed in liver tissue 12 h after the intraperitoneal administration of 100 or 200 µg flagellin (FliC) in a dose- and time-dependent manner in wild-type mice, but not in TLR5 KO mice. Deletion of the N-terminal or TLR5 binding domain of flagellin inhibited flagellin-induced inflammatory responses and the subsequent acute liver function abnormality and damage. These data confirmed that flagellin is an essential determinant of liver injury and demonstrated that the over-activation of TLR5 signaling by high-dose flagellin caused acute inflammatory responses, neutrophil accumulation and oxidative stress in the liver, which contributes to the progression and severity of flagellin-induced liver injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.