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Increased toxin-induced liver injury and fibrosis in interleukin-6-deficient mice
Open accessAbstract
Interleukin-6 null (IL-6−/−) mice have impaired liver regeneration and increased liver necrosis following partial hepatectomy that is corrected with IL-6 treatment. Following acute carbon tetrachloride (CCl 4) treatment, we found that IL-6−/− mice developed increased hepatocellular injury and defective regeneration with significant blunting of signal transducer-and-activator of transcription protein 3 (STAT3) and nuclear factor-κB (NF-κB) activation and reduced hepatocyte DNA synthetic and mitotic responses. After CCl 4 treatment, unlike partial hepatectomy, increased hepatocyte apoptosis was noted in IL-6−/− livers. Pretreatment with IL-6 before CCl 4 reduced acute CCl 4 injury and apoptosis and accelerated regeneration in both IL-6+/+ and −/− livers. Repetitive doses of CCl 4 in the presence or absence of phenobarbital resulted in increased injury and fibrosis in IL-6 −/− compared with +/+ livers. After acute and chronic injury, IL-6−/− livers showed the protracted presence of α-smooth muscle actin associated with activated stellate cells, indicating a disturbed response in wound healing that progressed to fibrosis. These data provide evidence for an important role for IL-6 in reducing CCl 4-induced acute and chronic liver injury and fibrosis.
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“Interestingly, several studies around 20 years ago have also shown that IL-6 protects hepatocytes from injuries.36,37”
From Kupffer-cell-derived IL-6 is repurposed for hepatocyte dedifferentiation via activating progenitor genes from injury-specific enhancers (2023) · cites this paper as [37]
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“Increasing evidence demonstrates that IL-6 has a protective role during liver injury.”
From The IL-6–gp130–STAT3 pathway in hepatocytes triggers liver protection in T cell–mediated liver injury (2005) · cites this paper as [2]
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Metadata
- Authors
- Kovalovich, K., DeAngelis, R. A., Li, W., Furth, E. E., Ciliberto, G., & Taub, R.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Taub, Rebecca
- Venue
- Hepatology
- Published
- 2000-01
- Volume
- 31
- Issue
- 1
- Pages
- 149-159
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2009008191
- Cited by
- 298
- References
- 56
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 11 · 2022: 8 · 2021: 6 · 2020: 5 · 2019: 4 · 2018: 8 · 2017: 13 · 2016: 13 · 2015: 9 · 2014: 11 · 2013: 11 · 2012: 12
- FWCI
- 17.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1k08dk002667-01, 5r01dk049629-05)
- National Institute of Diabetes and Digestive and Kidney Diseases (F32DK009732, DK-49629, 1 K08 DK 02667-01, 1 F32 DK09732-01)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Keywords
- interleukin-6, liver injury, liver fibrosis, carbon tetrachloride, hepatocyte apoptosis, liver regeneration, STAT3, NF-κB, hepatic stellate cells, alpha-smooth muscle actin, phenobarbital, hepatocyte DNA synthesis, wound healing
- MeSH terms
- Actins, Animals, Carbon Tetrachloride, DNA, DNA-Binding Proteins, Kinetics, Liver Cirrhosis, Experimental, Mice, Inbred C57BL, Mitosis, Phenobarbital, Trans-Activators, Interleukin-6, NF-kappa B, Apoptosis, Mice, Knockout, STAT3 Transcription Factor, Mice, Chemical and Drug Induced Liver Injury
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