ArticleThe Journal of biological chemistry2016
Toll-like Receptor 4 on Macrophage Promotes the Development of Steatohepatitis-related Hepatocellular Carcinoma in Mice.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 63 citations in OpenAlex.
- Ligature-induced periodontitis exacerbates high-carbohydrate/high-fat diet-induced fatty liver in mice under non-diabetic conditions.BMC oral health · 2026Article
- Bibliometric Analysis of Gut Microbiota and Hepatocellular Carcinoma: Research Trends and Frontiers.Journal of hepatocellular carcinoma · 2026Article
- Proinflammatory macrophages release CXCL5 to regulate T cell function and limit effects of αPD-1 in steatosis-driven liver cancer.JHEP reports : innovation in hepatology · 2025Article
- Gut Microbiota and Hepatocellular Carcinoma: Metabolic Products and Immunotherapy Modulation.Cancer medicine · 2025Review
- The Role of the Gut-Biliary-Liver Axis in Primary Hepatobiliary Liver Cancers: From Molecular Insights to Clinical Applications.Journal of personalized medicine · 2025Review
- Gut microbiota in liver diseases: initiation, development and therapy.Frontiers in medicine · 2025Review
- Trojan-Horse Strategy Targeting the Gut-Liver Axis Modulates Gut Microbiome and Reshapes Microenvironment for Orthotopic Hepatocellular Carcinoma Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Expression of modified FcγRI enables myeloid cells to elicit robust tumor-specific cytotoxicity.eLife · 2024Article
- Interplay of Extracellular Vesicles and TLR4 Signaling in Hepatocellular Carcinoma Pathophysiology and Therapeutics.Pharmaceutics · 2023Review
- The Role of TLR4 in the Immunotherapy of Hepatocellular Carcinoma: Can We Teach an Old Dog New Tricks?Cancers · 2023Review
- Article
- Pattern recognition receptors in the development of nonalcoholic fatty liver disease and progression to hepatocellular carcinoma: An emerging therapeutic strategy.Frontiers in endocrinology · 2023Review
- A metabolic associated fatty liver disease risk variant in MBOAT7 regulates toll like receptor induced outcomes.Nature communications · 2022Article
- Probiotics suppress nonalcoholic steatohepatitis and carcinogenesis progression in hepatocyte-specific PTEN knockout mice.Scientific reports · 2022Article
- Non-alcoholic fatty liver disease-related hepatocellular carcinoma: Is there a role for immunotherapy?World journal of gastroenterology · 2022Review
- Tumor-Associated Macrophages in Hepatocellular Carcinoma Pathogenesis, Prognosis and Therapy.Cancers · 2022Review
- Hepatic macrophage mediated immune response in liver steatosis driven carcinogenesis.Frontiers in oncology · 2022Review
- Animal Models of Hepatocellular Carcinoma: Current Applications in Clinical Research.Journal of hepatocellular carcinoma · 2022Review
- Hepatocellular Carcinoma: How the Gut Microbiota Contributes to Pathogenesis, Diagnosis, and Therapy.Frontiers in microbiology · 2022Review
- Toll-Like Receptor 4 Regulates Rabies Virus-Induced Humoral Immunity through Recruitment of Conventional Type 2 Dendritic Cells to Lymph Organs.Journal of virology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of Toll-like receptor (TLR) signaling has attracted much attention in the development of hepatic inflammation and hepatocellular carcinoma (HCC). We herein sought to determine the role of TLRs and responsible cells in steatohepatitis-related HCC. We used hepatocyte-specific Pten-deficient (Pten(Δ) (hep)) mice, which exhibit steatohepatitis followed by liver tumor formation, including HCC. We then generated Pten(Δ) (hep)/Tlr4(-/-) and Pten(Δ) (hep)/Tlr2(-/-) double-mutant mice and investigated the role of macrophages using reconstitution of bone marrow (BM)-derived cells, chemical depletion of macrophages, and isolated macrophages. Tlr4 but not Tlr2 deficiency in the Pten(Δ) (hep) mice suppressed tumor growth as well as hepatic inflammation. Gut sterilization by an antibiotic mixture reduced the portal LPS levels as well as tumor growth in the Pten(Δ) (hep) mice. Tumor growth was also decreased by reconstitution of BM-derived cells to Tlr4(-/-) BM cells. In addition, chemical depletion of macrophages significantly reduced tumor size and numbers. Macrophages expressing Ly6C were increased in number, which was associated with inflammation and tumor progression in the Pten(Δ) (hep) mice. Hepatic macrophages isolated from the Pten(Δ) (hep) mice abundantly expressed the Ly6C gene and produced much more IL-6 and TNFα in response to LPS. These proinflammatory cytokines induced the proliferation of HCC cells as well as oval cells, putative cancer progenitor cells. Indeed, putative cancer progenitor cells emerged before the development of macroscopic liver tumors and then increased in number under sustained inflammation. TLR4 on macrophages contributes to the development of steatohepatitis-related HCC in mice.
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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.