Loss of tolerance in C57BL/6 mice to the autoantigen E2 subunit of pyruvate dehydrogenase by a xenobiotic with ensuing biliary ductular disease

Kanji Wakabayashi, Zhe‐Xiong Lian, Patrick S.C. Leung, Yuki Moritoki, Koichi Tsuneyama, Mark J. Kurth, Kit S. Lam, Katsunori Yoshida, Guo‐Xiang Yang, Toshifumi Hibi, Aftab A. Ansari, William M. Ridgway, Ross L. Coppel, Ian R. Mackay, M. Eric Gershwin – 2 May 2008 – There have been important advances in defining effector mechanisms for several human autoimmune diseases. However, for most human autoimmune diseases, the induction stage is less well defined and there are very few clues on etiology.

Expression of X‐linked inhibitor‐of‐apoptosis protein in hepatocellular carcinoma promotes metastasis and tumor recurrence

Ying‐Hong Shi, Wen‐Xing Ding, Jian Zhou, Jun‐Yi He, Yang Xu, Andrea A. Gambotto, Hannah Rabinowich, Jia Fan, Xiao‐Ming Yin – 2 May 2008 – Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Despite significantly improved diagnosis and treatment in recent years, the long‐term therapeutic effect is compromised by the frequent recurrence and metastasis, of which the molecular mechanisms are not fully understood.

Mechanism of T cell tolerance induction by murine hepatic Kupffer cells

Qiang You, Linling Cheng, Ross M. Kedl, Cynthia Ju – 2 May 2008 – The liver is known to favor the induction of immunological tolerance rather than immunity. Although Kupffer cells (KC) have been indicated to play a role in liver tolerance to allografts and soluble antigens, the mechanisms involved remain unclear. We hypothesized that KCs could promote immune tolerance by acting as incompetent antigen‐presenting cells (APC), as well as actively suppressing T cell activation induced by other potent APCs.

Natural killer T cell dysfunction in CD39‐null mice protects against concanavalin A–induced hepatitis

Guido Beldi, Yan Wu, Yara Banz, Michael Nowak, Lindsay Miller, Keiichi Enjyoji, Arvand Haschemi, Gennady G. Yegutkin, Daniel Candinas, Mark Exley, Simon C. Robson – 2 May 2008 – Concanavalin A (Con A)–induced injury is an established natural killer T (NKT) cell–mediated model of inflammation that has been used in studies of immune liver disease. Extracellular nucleotides, such as adenosine triphosphate, are released by Con A–stimulated cells and bind to specific purinergic type 2 receptors to modulate immune activation responses.

Beyond insulin resistance: Innate immunity in nonalcoholic steatohepatitis

Jacquelyn J. Maher, Pablo Leon, James C. Ryan – 2 May 2008 – Obesity is an inflammatory disorder characterized by heightened activity of the innate immune system. Innate immune activation is central to the development of obesity‐related insulin resistance; it also plays an important role in obesity‐related tissue damage, such as that seen in atherosclerosis. Recent research has implicated the innate immune system in the pathophysiology of obesity‐related liver disease.

Genotype‐specific interactions of insulin resistance, steatosis, and fibrosis in chronic hepatitis C

Ian Homer Y. Cua, Jason M. Hui, James G. Kench, Jacob George – 2 May 2008 – The interaction between insulin resistance (IR), steatosis and genotype to fibrosis in chronic hepatitis C virus (HCV) infection has not been comprehensively assessed. We hypothesized that IR is a key mediator for the development of both steatosis and fibrosis in 346 untreated, nondiabetic patients solely infected with either genotype 1 or 3. We examined for genotype‐specific interactions between IR, steatosis and fibrosis by performing subgroup analyses.

Genetic polymorphism of hepatocyte nuclear factor‐4α influences human cytochrome P450 2D6 activity

Sang Seop Lee, Eun‐Young Cha, Hyun‐Ju Jung, Ji‐Hong Shon, Eun‐Young Kim, Chang‐Woo Yeo, Jae‐Gook Shin – 2 May 2008 – Hepatocyte nuclear factor‐4 alpha (HNF4A) is an essential transcriptional regulator for many genes that are expressed preferentially in the liver. Among the important functions of the liver is drug metabolism in response to xenobiotic exposure. Recent studies have suggested that HNF4A regulates the expression of cytochrome P450 (CYP), including CYP2D6 and CYP3A4, which show large individual variations in their activities.

Pathogenic role of natural killer T and natural killer cells in acetaminophen‐induced liver injury in mice is dependent on the presence of dimethyl sulfoxide

Mary Jane Masson, Leah D. Carpenter, Mary L. Graf, Lance R. Pohl – 2 May 2008 – Dimethyl sulfoxide (DMSO) is commonly used in biological studies to dissolve drugs and enzyme inhibitors with low solubility. Although DMSO is generally thought of as being relatively inert, it can induce biological effects that are often overlooked.

Subscribe to