ArticlePloS one2016
TLR4-Dependent Secretion by Hepatic Stellate Cells of the Neutrophil-Chemoattractant CXCL1 Mediates Liver Response to Gut Microbiota.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Inflammatory gut-liver crosstalk: mechanisms and therapeutic targets.Experimental & molecular medicine · 2026Review
- Chemokines and chemokine receptors in metabolic dysfunction-associated steatohepatitis: pathogenic mechanisms and clinical implications.Cellular & molecular biology letters · 2026Review
- Geranylgeranoic acid, toll-like receptor 4, and pyroptosis-related signaling in hepatocellular carcinoma: a hypothesis-generating perspective.Oncology reviews · 2026Article
- The high efficiency protective effectiveness of a newly isolated myoviruses bacteriophage vB_AceP_PAc in protecting mice from Aeromonas caviae infection in mice.BMC microbiology · 2025Article
- Inflammatory markers as predictors of liver fibrosis in type 2 diabetes patients with metabolic dysfunction-associated fatty liver disease.Frontiers in endocrinology · 2025Article
- A narrative review of chemokine receptors CXCR1 and CXCR2 and their role in acute respiratory distress syndrome.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Plasticity, heterogeneity, and multifunctionality of hepatic stellate cells in liver pathophysiology.Hepatology communications · 2024Review
- The Clinical Significance and Involvement in Molecular Cancer Processes of Chemokine CXCL1 in Selected Tumors.International journal of molecular sciences · 2024Review
- Immunology of gut microbiome and liver in non-alcoholic fatty liver disease (NAFLD): mechanisms, bacteria, and novel therapeutic targets.Archives of microbiology · 2024Review
- Bioinformatic Analysis of the CXCR2 Ligands in Cancer Processes.International journal of molecular sciences · 2023Article
- Commensal gut microbiota-based strategies for oral delivery of therapeutic proteins.Trends in pharmacological sciences · 2022Review
- The Importance of CXCL1 in the Physiological State and in Noncancer Diseases of the Oral Cavity and Abdominal Organs.International journal of molecular sciences · 2022Review
- Gut microbiome in non-alcoholic fatty liver disease associated hepatocellular carcinoma: Current knowledge and potential for therapeutics.World journal of gastrointestinal oncology · 2022Review
- Article
- Review
- Regulation and functional roles of chemokines in liver diseases.Nature reviews. Gastroenterology & hepatology · 2021Review
- Super enhancer regulation of cytokine-induced chemokine production in alcoholic hepatitis.Nature communications · 2021Article
- Spatiotemporally specific roles of TLR4, TNF, and IL-17A in murine endotoxin-induced inflammation inferred from analysis of dynamic networks.Molecular medicine (Cambridge, Mass.) · 2021Article
- Gut Microbiome Directs Hepatocytes to Recruit MDSCs and Promote Cholangiocarcinoma.Cancer discovery · 2021Article
- Inhibition of 5-Lipoxygenase in Hepatic Stellate Cells Alleviates Liver Fibrosis.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsThe gut microbiota significantly influences hepatic immunity. Little is known on the precise mechanism by which liver cells mediate recognition of gut microbes at steady state. Here we tested the hypothesis that a specific liver cell population was the sensor and we aimed at deciphering the mechanism by which the activation of TLR4 pathway would mediate liver response to gut microbiota.
methodsUsing microarrays, we compared total liver gene expression in WT versus TLR4 deficient mice. We performed in situ localization of the major candidate protein, CXCL1. With an innovative technique based on cell sorting, we harvested enriched fractions of KCs, LSECs and HSCs from the same liver. The cytokine secretion profile was quantified in response to low levels of LPS (1ng/mL). Chemotactic activity of stellate cell-derived CXCL1 was assayed in vitro on neutrophils upon TLR4 activation.
resultsTLR4 deficient liver had reduced levels of one unique chemokine, CXCL1 and subsequent decreased of neutrophil counts. Depletion of gut microbiota mimicked TLR4 deficient phenotype, i.e., decreased neutrophils counts in the liver. All liver cells were responsive to low levels of LPS, but hepatic stellate cells were the major source of chemotactic levels of CXCL1. Neutrophil migration towards secretory hepatic stellate cells required the TLR4 dependent secretion of CXCL1.
conclusionsShowing the specific activation of TLR4 and the secretion of one major functional chemokine-CXCL1, the homolog of human IL-8-, we elucidate a new mechanism in which Hepatic Stellate Cells play a central role in the recognition of gut microbes by the liver at steady state.
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