ArticleThe American journal of pathology2000
The development and compensation of biliary cirrhosis in interleukin-6-deficient mice.
Article in The American journal of pathology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 102 citations in OpenAlex.
- LGALS3 marks a pro-inflammatory, efferocytosis-low hepatic macrophage state and promotes hepatic stellate cell activation through the candidate receptor ANXA2 in liver cirrhosis.Frontiers in immunology · 2026Article
- Sodium taurocholate promotes liver regeneration after portal vein ligation in rats.Scientific reports · 2025Article
- Establishment of a mouse model for bile duct repair and tissue engineering.Experimental and therapeutic medicine · 2022Article
- The two facets of gp130 signalling in liver tumorigenesis.Seminars in immunopathology · 2021Review
- Review
- Network Pharmacology-Based Investigation of the Therapeutic Mechanisms of Action of Danning Tablets in Nonalcoholic Fatty Liver Disease.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Comparing distress of mouse models for liver damage.Scientific reports · 2020Article
- RTK signaling requires C3ar1/C5ar1 and IL-6R joint signaling to repress dominant PTEN, SOCS1/3 and PHLPP restraint.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Significance of IL-6 Deficiency in Recognition Memory in Young Adult and Aged Mice.Behavior genetics · 2019Article
- Effect of the transdifferentiation of BECs into myofibroblasts on the pathogenesis of secondary cholestatic hepatic fibrosis.Experimental and therapeutic medicine · 2019Article
- VEGFR2 survival and mitotic signaling depends on joint activation of associated C3ar1/C5ar1 and IL-6R-gp130.Journal of cell science · 2019Article
- Inflammation and the Gut-Liver Axis in the Pathophysiology of Cholangiopathies.International journal of molecular sciences · 2018Review
- The STAT3-IL-10-IL-6 Pathway Is a Novel Regulator of Macrophage Efferocytosis and Phenotypic Conversion in Sterile Liver Injury.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- The Cholangiocyte Adenosine-IL-6 Axis Regulates Survival During Biliary Cirrhosis.Gene expression · 2017Article
- Epidermal growth factor signaling protects from cholestatic liver injury and fibrosis.Journal of molecular medicine (Berlin, Germany) · 2017Article
- Inhibition of notch signaling pathway prevents cholestatic liver fibrosis by decreasing the differentiation of hepatic progenitor cells into cholangiocytes.Laboratory investigation; a journal of technical methods and pathology · 2016Article
- Interleukin‑6 induces epithelial‑mesenchymal transition in human intrahepatic biliary epithelial cells.Molecular medicine reports · 2016Article
- Mice with Hepatic Loss of the Desmosomal Protein γ-Catenin Are Prone to Cholestatic Injury and Chemical Carcinogenesis.The American journal of pathology · 2015Article
- Interactions between Myc and Mediators of Inflammation in Chronic Liver Diseases.Mediators of inflammation · 2015Review
- Cytokine single nucleotide polymorphisms in patients' with gallstone: dose TGF-β gene variants affect gallstone formation?Molecular biology reports · 2013Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
In an effort to understand the role of IL-6/gp130 signaling in chronic liver injury, IL-6 deficient (IL-6(-/-)) and wild-type control (IL-6(+/+)) mice were subjected to bile duct ligation (BDL) for 12 weeks. This maneuver causes chronic biomechanical stress and liver injury, fueling sustained biliary epithelial and hepatocyte proliferation. By 12 weeks after BDL, IL-6(-/-) mice develop significantly higher total serum bilirubin levels (23.2 +/- 2.3 versus 14.9 +/- 2.1 mg/dl, P < 0.0001; delta bilirubin subfraction 16.7 +/- 4.0% versus 9.2 +/- 1.8%; P < 0.002), and the majority (15/18) show "black" gallbladder bile, compared to IL-6(+/+) mice (5/16; P < 0.003). The IL-6(-/-) mice also cannot sustain the compensatory liver mass increase commonly seen with chronic obstructive cholangiopathy, because of less hepatocyte proliferation, despite a rate of hepatocyte apoptosis similar to that of IL-6(+/+) mice. Moreover, IL-6(-/-) mice show a more advanced stage of biliary fibrosis and a higher mortality rate than the IL-6(+/+) controls (51% versus 23%; P < 0.02). These phenotypic changes in the IL-6(-/-) mice are associated with decreased expression and phosphorylation of gp130 and the transcription factor STAT3, compared to IL-6(+/+) mice. Daily treatment with exogenous recombinant IL-6 for 3-6 weeks starting at 6 weeks after BDL significantly lowers the serum total bilirubin in both groups. In the IL-6(-/-) mice, exogenous IL-6 treatment also increases the level of gp130 protein expression and completely reverses the loss of liver mass by increasing the hepatocyte proliferation. In conclusion, IL-6 appears to contribute to biliary tree integrity and maintenance of hepatocyte mass during chronic injury.
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