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IL‐20 and IL‐20R1 antibodies protect against liver fibrosis
Author(s) -
Chiu YiShu,
Wei ChiChen,
Lin YihJyh,
Hsu YuHsiang,
Chang MingShi
Publication year - 2014
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.27189
Subject(s) - hepatic stellate cell , liver injury , proinflammatory cytokine , cytokine , ccl4 , cirrhosis , hepatocyte , fibrosis , medicine , biology , cancer research , immunology , pathology , endocrinology , chemistry , inflammation , carbon tetrachloride , biochemistry , organic chemistry , in vitro
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. (H epatology 2014;60:1003–1014)