ArticleJournal of pharmaceutical sciences2016
Co-culture of Hepatocytes and Kupffer Cells as an In Vitro Model of Inflammation and Drug-Induced Hepatotoxicity.
Article in Journal of pharmaceutical sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 94 citations in OpenAlex.
- Article
- Alternatives to animal models in gastroenterology and hepatology research.Frontiers in pharmacology · 2026Review
- 3D co-cultures of primary human hepatocytes and Kupffer-like cells to address innate immune responses to rAAV.Scientific reports · 2025Article
- Novel emerging cell and organoid systems for the study of drug metabolism and toxicity in humans.Drug metabolism and disposition: the biological fate of chemicals · 2025Review
- The Evolution of Cell Culture Systems to Study Hepatitis B Virus Pathogenesis and Antiviral Susceptibility.Viruses · 2025Review
- Advancing hepatotoxicity assessment: current advances and future directions.Toxicological research · 2025Review
- Vagus nerve modulates acute-on-chronic liver failure progression via CXCL9.Chinese medical journal · 2025Article
- Investigation on ABCC6-Deficient Human Hepatocytes Generated by CRISPR-Cas9 Genome Editing.Cells · 2025Article
- A new human autologous hepatocyte/macrophage co-culture system that mimics drug-induced liver injury-like inflammation.Archives of toxicology · 2025Article
- HIVIL: A humanNAM journal · 2025Article
- The Long-Term Impact of Polysaccharide-Coated Iron Oxide Nanoparticles on Inflammatory-Stressed Mice.Journal of xenobiotics · 2024Article
- Exosomes regulate SIRT3-related autophagy by delivering miR-421 to regulate macrophage polarization and participate in OSA-related NAFLD.Journal of translational medicine · 2024Article
- In Vitro Hepatotoxicity of Routinely Used Opioids and Sedative Drugs.Current issues in molecular biology · 2024Article
- Vascularized Hepatocellular Carcinoma on a Chip to Control Chemoresistance through Cirrhosis, Inflammation and Metabolic Activity.Small structures · 2023Article
- Review
- An Immunological Perspective on the Mechanism of Drug Induced Liver Injury: Focused on Drugs for Treatment of Hepatocellular Carcinoma and Liver Transplantation.International journal of molecular sciences · 2023Review
- Performance assessment and economic analysis of a human Liver-Chip for predictive toxicology.Communications medicine · 2022Article
- Resident Macrophages and Their Potential in Cardiac Tissue Engineering.Tissue engineering. Part B, Reviews · 2022Review
- Exploiting maleimide-functionalized hyaluronan hydrogels to test cellular responses to physical and biochemical stimuli.Biomedical materials (Bristol, England) · 2022Article
- The Role of Cytochrome P450 Enzymes in COVID-19 Pathogenesis and Therapy.Frontiers in pharmacology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Immune-mediated drug-induced hepatotoxicity is often unrecognized as a potential mode of action due to the lack of appropriate in vitro models. We have established an in vitro rat donor-matched hepatocyte and Kupffer cell co-culture (HKCC) model to study immune-related responses to drug exposure. Optimal cell culture conditions were identified for the maintenance of co-cultures based on cell longevity, monolayer integrity, and cytokine response after lipopolysaccharide (LPS) exposure. Hepatocyte monocultures and HKCCs were then used to test a subset of compounds associated with hepatotoxic effects with or without LPS. Cytokine levels and metabolic activity (cytochrome P450 3A [Cyp3A]) were measured after a 48-h exposure to monitor endotoxin-induced changes in acute phase and functional end points. LPS-activated HKCCs, but not hepatocyte monocultures, treated with trovafloxacin or acetaminophen, compounds associated with immune-mediated hepatotoxicity, showed LPS-dependent decreases in interleukin-6 production with concomitant increases in Cyp3A activity. Differential endotoxin- and model-dependent alterations were observed in cytokine profiles and Cyp3A activity levels that corresponded to specific compounds. These results indicate the utility of the HKCC model system to discern compound-specific effects that may lead to enhanced or mitigate hepatocellular injury due to innate or adaptive immune responses.
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What OpenQuestion holds
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.