Dietary factors alter hepatic innate immune system in mice with nonalcoholic fatty liver disease

Zhiping Li, Mark J. Soloski, Anna Mae Diehl – 20 September 2005 – Dietary factors promote obesity and obesity‐related disorders, such as fatty liver disease. Natural killer T (NKT) cells are components of the innate immune system that regulate proinflammatory (Th‐1) and anti‐inflammatory (Th‐2) immune responses.

CTLA‐4Ig suppresses liver injury by inhibiting acquired immune responses in a mouse model of fulminant hepatitis

Yasuhiro Nakayama, Yukihiro Shimizu, Katsuharu Hirano, Kazumi Ebata, Masami Minemura, Akiharu Watanabe, Toshiro Sugiyama – 20 September 2005 – Expression of costimulatory molecules is significantly upregulated in various organs in an animal model of severe hepatitis induced by injection of Propionibacterium acnes (P. acnes) and lipopolysaccharide (LPS). In the present study, we examined whether blockade of costimulatory signals by CTLA‐4Ig can suppress the liver injury in this model.

Cholesterol accumulation and liver cell death in mice with Niemann‐Pick type C disease

Eduardo P. Beltroy, James A. Richardson, Jay D. Horton, Stephen D. Turley, John M. Dietschy – 20 September 2005 – Niemann‐Pick type C (NPC) disease develops as a result of mutations in the NPC1 gene that encodes a protein involved in the net movement of unesterified cholesterol from the late endosomal/lysosomal compartment to the metabolically active pool of sterol in the cytosol of virtually every cell in the body.

Intrahepatic CD8+ T‐cell failure during chronic hepatitis C virus infection

Hans Christian Spangenberg, Sergei Viazov, Nadine Kersting, Christoph Neumann‐Haefelin, Denise McKinney, Michael Roggendorf, Fritz von Weizsäcker, Hubert E. Blum, Robert Thimme – 20 September 2005 – The precise mechanisms responsible for the failure of intrahepatic hepatitis C virus (HCV)‐specific CD8+ T cells to control the virus during persistent infection have not been fully defined. We therefore studied the CD8+ T‐cell response in 27 HLA‐A2–positive patients using four previously well‐defined HLA‐A2–restricted HCV epitopes.

Hepatitis C virus inhibits intracellular interferon alpha expression in human hepatic cell lines

Ting Zhang, Rong‐Tuan Lin, Yuan Li, Steven D. Douglas, Catherine Maxcey, Chun Ho, Jian‐Ping Lai, Yan‐Jian Wang, Qi Wan, Wen‐Zhe Ho – 20 September 2005 – The chronicity of hepatitis C virus (HCV) infection raises the question of how HCV is able to persist in hepatic cells. We show that human primary hepatocytes and human hepatic cell lines (Huh7 and HepG2) spontaneously produce interferon (IFN)‐α that is inhibited in the HCV replicon cells (Huh.8 and FCA‐1).

Fibroblast activation protein increases apoptosis, cell adhesion, and migration by the LX‐2 human stellate cell line

Xin Maggie Wang, Denise Ming Tse Yu, Geoffrey W. McCaughan, Mark D. Gorrell – 20 September 2005 – Injury and repair in chronic liver disease involve cell adhesion, migration, apoptosis, proliferation, and a wound healing response. In liver, fibroblast activation protein (FAP) has both collagenase and dipeptidyl peptidase IV (DPIV) activities and is expressed only by activated hepatic stellate cells (HSC) and myofibroblasts, which produce and degrade extracellular matrix (ECM). FAP was colocalized with collagen fibers, fibronectin, and collagen type I in human liver.

Endocannabinoids promote hepatic lipogenesis and steatosis through CB1 receptors

Robert F. Schwabe – 20 September 2005 – Endogenous cannabinoids acting at CB1 receptors stimulate appetite, and CB1 antagonists show promise in the treatment of obesity. CB1−/− mice are resistant to diet‐induced obesity even though their caloric intake is similar to that of wild‐type mice, suggesting that endocannabinoids also regulate fat metabolism. Here, we investigated the possible role of endocannabinoids in the regulation of hepatic lipogenesis.

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