Cited by 77Liver physiology and pathologyDrug-Induced Hepatotoxicity and ProtectionLiver Disease Diagnosis and Treatment

IL‐20 and IL‐20R1 antibodies protect against liver fibrosis

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Chiu, Yi-Shu, Wei, Chi-Chen, Lin, Yih-Jyh, Hsu, Yu-Hsiang, Chang, Ming-Shi·2014·Hepatology

Abstract

Interleukin (IL)-20 is a proinflammatory cytokine of the IL-10 family and involved in rheumatoid arthritis, atherosclerosis, stroke, and osteoporosis. However, the pathophysiological roles of IL-20 in liver injury have not been extensively studied. We explored the involvement of IL-20 in liver injury and the therapeutic potential of IL-20 antagonists for treating liver fibrosis. Compared with normal liver tissue from healthy individuals, the amount of IL-20 was much higher in hepatocytes and hepatic stellate cells in liver biopsies from patients with fibrosis, cirrhosis, and hepatocellular carcinoma. Carbon tetrachloride (CCl 4) treatment induced IL-20 that further up-regulated the expression of transforming growth factor (TGF)-β1 and p21 WAF1 and resulted in cell cycle arrest in the Clone-9 rat hepatocyte cell line. IL-20 activated quiescent rat hepatic stellate cells (HSCs) and up-regulated TGF-β1 expression. IL-20 also increased TGF-β1, tumor necrosis factor (TNF)-α, and type I collagen (Col-I) expression, and promoted the proliferation and migration of activated HSCs. Serum IL-20 was significantly elevated in mice with short-term and long-term CCl 4-induced liver injury. In mice with short-term liver injury, anti-IL-20 monoclonal antibody (7E) and anti-IL-20 receptor (IL-20R1) monoclonal antibody (51D) attenuated hepatocyte damage caused by CCl 4, TGF-β1, and chemokine production. In mice with long-term liver injury, 7E and 51D inhibited CCl 4-induced cell damage, TGF-β1 production, liver fibrosis, HSC activation, and extracellular matrix accumulation, which was caused by the reduced expression of tissue inhibitors of metalloproteinases as well as increased metalloproteinase expression and Col-I production. IL-20R1-deficient mice were protected from short-term and long-term liver injury. Conclusion: We identified a pivotal role of IL-20 in liver injury and showed that 7E and 51D may be therapeutic for liver fibrosis. (Hepatology 2014;60:1003–1014)

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  • Cytokine-mediated activation is indispensable for HSC profibrotic functions.

    “Multiple mechanisms have been implicated in HSC profibrotic functions, but cytokine‐mediated activation is indispensable.( 72 )”

    From The Emerging Role of B Cells in the Pathogenesis of NAFLD (2021) · cites this paper as [72]

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Research works printed but not linked: 2

  1. Wynn TA. Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat Rev Immunol 2004;4:583-594.
  2. Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB. Interleu- kin-10 and related cytokines and receptors. Annu Rev Immunol 2004; 22:929-979.

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Authors
Chiu, Y.-S., Wei, C.-C., Lin, Y.-J., Hsu, Y.-H., & Chang, M.-S.
Affiliations
National Cheng Kung University (TW)
Corresponding author
Chang, Ming-Shi
Venue
Hepatology
Published
2014-09
Volume
60
Issue
3
Pages
1003-1014
ISSN
0270-9139 (ISSN-L)
OpenAlex
W2119403715
Cited by
77
References
35
Citations by year
2026: 1 · 2025: 2 · 2024: 12 · 2023: 4 · 2022: 9 · 2021: 9 · 2020: 12 · 2019: 6 · 2018: 5 · 2017: 6 · 2016: 1 · 2015: 8 · 2014: 2
FWCI
3.17
Type
journal article
Language
en
Open access
Locations
  • Hepatology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Cheng Kung University
  • Taichung Veterans General Hospital
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
Keywords
IL-20, liver fibrosis, hepatocyte injury, hepatic stellate cells, TGF-β1, carbon tetrachloride, extracellular matrix accumulation, tissue inhibitors of metalloproteinases, type I collagen, hepatocellular carcinoma, liver cirrhosis
MeSH terms
Animals, Antibodies, Monoclonal, Carbon Tetrachloride Poisoning, Cell Line, Disease Models, Animal, Humans, Interleukins, Liver Cirrhosis, Male, Mice, Inbred C57BL, Case-Control Studies, Rats, Sprague-Dawley, Receptors, Interleukin, Mice, Rats, Chemical and Drug Induced Liver Injury

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