BACKGROUND/AIMS: Several previous studies have suggested that interferon gamma (IFNgamma) may play a key role during hepatic progenitor cell (HPC) mediated liver regeneration. However to date, no studies have directly tested the ability of IFNgamma to mediate the HPC response in an in vivo model. METHODS/ RESULTS: Administration of IFNgamma to mice receiving a choline deficient, ethionine (CDE) supplemented diet to induce chronic injury resulted in an augmented HPC response. This was accompanied by increased inflammation, altered cytokine expression and hepatic fibrosis. Serum alanine aminotransferase activity, hepatocyte apoptosis and Bak staining were significantly increased in IFNgamma-treated, CDE-fed mice, demonstrating that liver damage was exacerbated in these animals. Administration of IFNgamma to control diet fed mice did not induce liver damage, however it did stimulate hepatic inflammation. CONCLUSIONS: Our results suggest that IFNgamma increases the HPC response to injury by stimulating hepatic inflammation and aggravating liver damage. This is accompanied by an increase in hepatic fibrogenesis, supporting previous reports which suggest that the HPC response may drive fibrogenesis during chronic liver injury.
BACKGROUND/AIMS: Several previous studies have suggested that interferon gamma (IFNgamma) may play a key role during hepatic progenitor cell (HPC) mediated liver regeneration. However to date, no studies have directly tested the ability of IFNgamma to mediate the HPC response in an in vivo model. METHODS/ RESULTS: Administration of IFNgamma to mice receiving a choline deficient, ethionine (CDE) supplemented diet to induce chronic injury resulted in an augmented HPC response. This was accompanied by increased inflammation, altered cytokine expression and hepatic fibrosis. Serum alanine aminotransferase activity, hepatocyte apoptosis and Bak staining were significantly increased in IFNgamma-treated, CDE-fed mice, demonstrating that liver damage was exacerbated in these animals. Administration of IFNgamma to control diet fed mice did not induce liver damage, however it did stimulate hepatic inflammation. CONCLUSIONS: Our results suggest that IFNgamma increases the HPC response to injury by stimulating hepatic inflammation and aggravating liver damage. This is accompanied by an increase in hepatic fibrogenesis, supporting previous reports which suggest that the HPC response may drive fibrogenesis during chronic liver injury.
Authors: Igor M V M Madeira; Debora M O Pereira; Aline A Sousa; Cesar A Vilela; Izabela F G Amorim; Marcelo V Caliari; Carolina C Souza; Wagner L Tafuri Journal: Int J Exp Pathol Date: 2016-05-31 Impact factor: 1.925
Authors: Felix Heymann; Linda Hammerich; Dunja Storch; Matthias Bartneck; Sebastian Huss; Vanessa Rüsseler; Nikolaus Gassler; Sergio A Lira; Tom Luedde; Christian Trautwein; Frank Tacke Journal: Hepatology Date: 2012-01-13 Impact factor: 17.425
Authors: Hong-lei Weng; De-chun Feng; Svetlana Radaeva; Xiao-ni Kong; Lei Wang; Yan Liu; Qi Li; Hong Shen; Yun-peng Gao; Roman Müllenbach; Stefan Munker; Tong Huang; Jia-lin Chen; Vincent Zimmer; Frank Lammert; Peter R Mertens; Wei-min Cai; Steven Dooley; Bin Gao Journal: J Hepatol Date: 2013-06-04 Impact factor: 25.083