The authors
thank the Cellular and Molecular Morphology Core of the Texas Medical Center Digestive Diseases Center (NIDDK-P30-DK056338) and Pamela Parsons for help with immunohistochemistry, the Clinical Pathology Laboratory of Texas Children Hospital for liver function tests, and Dr. Juan Marini (BCM) for help with submandibular bleeding. Additional Supporting Information may be found in the online version of this article. “
“Interleukin (IL)-20 is a proinflammatory cytokine of the IL-10 family and involved in rheumatoid arthritis, atherosclerosis, stroke, and osteoporosis. However, the pathophysiological Ceritinib 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 p21WAF1 and resulted in cell cycle arrest in the Clone-9 rat hepatocyte cell line.
IL-20 activated quiescent rat hepatic stellate cells (HSCs) and HSP inhibitor 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 check details 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) “
“We tested the hypothesis that the pathogenesis of alcoholic liver injury is mediated by epigenetic changes in regulatory genes that result from the induction of aberrant methionine metabolism by ethanol feeding. Five-month-old cystathionine beta synthase heterozygous and wild-type C57BL/6J littermate mice were fed liquid control or ethanol diets by intragastric infusion for 4 weeks.