IL-20 and IL-20R1 antibodies protect against liver fibrosis.

Abstract

UNLABELLED:

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 (CCl4) 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 CCl4 -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 CCl4, TGF-β1, and chemokine production. In mice with long-term liver injury, 7E and 51D inhibited CCl4 -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.

• Authors: Yi-Shu Chiu, Chi-Chen Wei, Yih-Jyh Lin, Yu-Hsiang Hsu, Ming-Shi Chang
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 60 Issue 3 Pg. 1003-14 (Sep 2014) ISSN: 1527-3350 [Electronic] United States
• PMID: 24763901 (Publication Type: Journal Article)
• Copyright: © 2014 by the American Association for the Study of Liver Diseases.

Chemical References

• Antibodies, Monoclonal
• Interleukins
• Receptors, Interleukin
• interleukin-20 receptor
• interleukin 20

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• Carbon Tetrachloride Poisoning (complications, metabolism)
• Case-Control Studies
• Cell Line
• Chemical and Drug Induced Liver Injury (complications, metabolism)
• Disease Models, Animal
• Humans
• Interleukins (antagonists & inhibitors, immunology, metabolism)
• Liver Cirrhosis (etiology, immunology, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Rats
• Rats, Sprague-Dawley
• Receptors, Interleukin (immunology, metabolism)