ArticleHepatology (Baltimore, Md.)2015
Liver is the major source of elevated serum lipocalin-2 levels after bacterial infection or partial hepatectomy: a critical role for IL-6/STAT3.
Article in Hepatology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 1 of them a synthesis that pooled it.
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Who cites it
101 citing papers in PubMed, 1 synthesis or guideline pooled it, 176 citations in OpenAlex.
- Urine Interleukin 18 and Lipocalin 2 Are Biomarkers of Acute Tubular Necrosis in Patients With Cirrhosis: A Systematic Review and Meta-analysis.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2017Pooled it
- Microbial metabolite Enterobactin impairs mitochondrial respiration and alleviates colitis.Gut microbes · 2026Article
- Cyclin D1 regulates the hepatic response to feeding: Evidence for non-cell cycle roles in the liver.bioRxiv : the preprint server for biology · 2026Article
- Hippocampal Lipocalin-2 in T2DM Associated Neurodegeneration: A Therapeutic Perspective.Neurochemical research · 2026Review
- Mechanisms and Therapeutic Potential of Nutritional Immunity.Pathogens (Basel, Switzerland) · 2026Review
- Human Liver Organoids as an Experimental Tool to Investigate Lipocalin-2 in Hepatic Inflammation.Cells · 2026Article
- Article
- Liver as a key organ for systemic antimicrobial defense.Hepatology communications · 2025Review
- 17β-Trenbolone Increases the Release of Lipocalin 2 via the Brain-Liver Axis and Causes Alzheimer's Disease-Like Symptoms in CSDS-Induced Mice.Molecular neurobiology · 2025Article
- Y665F variant of mouse Stat5b protects against acute kidney injury through transcriptomic shifts in renal gene expression.Scientific reports · 2025Article
- Iron Deficiency Impairs Dendritic Cell Development and Function, Compromising Host Anti-Infection Capacity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Procalcitonin levels in septic and nonseptic subjects with AKI and ESKD prior to and during continuous kidney replacement therapy (CKRT).Critical care (London, England) · 2025Article
- Immunology and treatments of fatty liver disease.Archives of toxicology · 2025Review
- Luteolin improves precancerous conditions of the gastric mucosa by binding STAT3 and inhibiting LCN2 expression.International journal of biological sciences · 2025Article
- Chitinase 3-like protein 1 deficiency ameliorates drug-induced acute liver injury by inhibition of neutrophil recruitment through lipocalin-2.Frontiers in pharmacology · 2025Article
- From "immune silence" to "immune dialogue": modification strategies for bone substitutes based on bone immunomodulatory characteristics.Frontiers in cell and developmental biology · 2025Review
- Article
- Lipocalin-2 and intestinal diseases.World journal of gastroenterology · 2024Review
- Can Novel Biomarkers Effectively Predict Acute Kidney Injury in Liver or Kidney Transplant Recipients?International journal of molecular sciences · 2024Review
- Pre-metastatic niche: formation, characteristics and therapeutic implication.Signal transduction and targeted therapy · 2024Review
41 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 10 institutions in 5 countries.
Funding
Abstract
unlabelledLipocalin-2 (LCN2) was originally isolated from human neutrophils and termed neutrophil gelatinase-associated lipocalin (NGAL). However, the functions of LCN2 and the cell types that are primarily responsible for LCN2 production remain unclear. To address these issues, hepatocyte-specific Lcn2 knockout (Lcn2(Hep-/-)) mice were generated and subjected to bacterial infection (with Klesbsiella pneumoniae or Escherichia coli) or partial hepatectomy (PHx). Studies of Lcn2(Hep-/-) mice revealed that hepatocytes contributed to 25% of the low basal serum level of LCN2 protein (∼ 62 ng/mL) but were responsible for more than 90% of the highly elevated serum LCN2 protein level (∼ 6,000 ng/mL) postinfection and more than 60% post-PHx (∼ 700 ng/mL). Interestingly, both Lcn2(Hep-/-) and global Lcn2 knockout (Lcn2(-/-)) mice demonstrated comparable increases in susceptibility to infection with K. pneumoniae or E. coli. These mice also had increased enteric bacterial translocation from the gut to the mesenteric lymph nodes and exhibited reduced liver regeneration after PHx. Treatment with interleukin (IL)-6 stimulated hepatocytes to produce LCN2 in vitro and in vivo. Hepatocyte-specific ablation of the IL-6 receptor or Stat3, a major downstream effector of IL-6, markedly abrogated LCN2 elevation in vivo. Furthermore, chromatin immunoprecipitation (ChIP) assay revealed that STAT3 was recruited to the promoter region of the Lcn2 gene upon STAT3 activation by IL-6.
conclusionHepatocytes are the major cell type responsible for LCN2 production after bacterial infection or PHx, and this response is dependent on IL-6 activation of the STAT3 signaling pathway. Thus, hepatocyte-derived LCN2 plays an important role in inhibiting bacterial infection and promoting liver regeneration.
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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.