CCR5 deficiency exacerbates T‐cell–mediated hepatitis in mice

Christophe Moreno, Thierry Gustot, Charles Nicaise, Eric Quertinmont, Nathalie Nagy, Marc Parmentier, Olivier Le Moine, Jacques Devière, Hubert Louis – 20 September 2005 – Experimental T‐cell–mediated hepatitis induced by concanavalin A (Con A) involves the production of different cytokines and chemokines and is characterized by leukocyte infiltration. Because the chemokine receptor CCR5 and its ligands (CCL3, CCL4, and CCL5) regulate leukocyte chemotaxis and activation, we investigated the role of CCR5 during Con A–induced liver injury.

Antioxidative function of L‐FABP in L‐FABP stably transfected Chang liver cells

Guqi Wang, Yuewen Gong, Judy Anderson, Dongfeng Sun, Gerald Minuk, Michael S. Roberts, Frank J. Burczynski – 20 September 2005 – Liver fatty acid binding protein (L‐FABP) contains amino acids that are known to possess antioxidant function. In this study, we tested the hypothesis that L‐FABP may serve as an effective endogenous cytoprotectant against oxidative stress. Chang liver cells were selected as the experimental model because of their undetectable L‐FABP mRNA level. Full‐length L‐FABP cDNA was subcloned into the mammalian expression vector pcDNA3.1 (pcDNA‐FABP).

Nuclear translocation of UDCA by the glucocorticoid receptor is required to reduce TGF‐β1–induced apoptosis in rat hepatocytes

Susana Solá, Joana D. Amaral, Rui E. Castro, Rita M. Ramalho, Pedro M. Borralho, Betsy T. Kren, Hirotoshi Tanaka, Cifford J. Steer, Cecília M. P. Rodrigues – 20 September 2005 – Ursodeoxycholic acid (UDCA) inhibits classical mitochondrial pathways of apoptosis by either directly stabilizing mitochondrial membranes or modulating specific upstream targets. Furthermore, UDCA regulates apoptosis‐related genes from transforming growth factor β1 (TGF‐β1)–induced hepatocyte apoptosis by a nuclear steroid receptor (NSR)–dependent mechanism.

Reduced susceptibility to cholesterol gallstone formation in mice that do not produce apolipoprotein B48 in the intestine

Helen H. Wang, David Q.‐H. Wang – 20 September 2005 – It has been found that polymorphisms in the apolipoprotein (APO)‐B gene are associated with cholesterol gallstones in humans. We hypothesized that APO‐B plays a major regulatory role in the response of biliary cholesterol secretion to high dietary cholesterol and contributes to cholesterol gallstone formation.

Altered monocyte responses to defined TLR ligands in patients with primary biliary cirrhosis

Tin Ky Mao, Zhe‐Xiong Lian, Carlo Selmi, Yasunori Ichiki, Paul Ashwood, Aftab A. Ansari, Ross L. Coppel, Shinji Shimoda, Hiromi Ishibashi, M. Eric Gershwin – 20 September 2005 – The role of the adaptive immune response, with regard to the development of autoantibodies, has been extensively studied in primary biliary cirrhosis (PBC). However, the importance of innate immunity has been noted only recently.

Genome‐wide response of the human Hep3B hepatoma cell to proinflammatory cytokines, from transcription to translation

Cédric Coulouarn, Grégory Lefebvre, Romain Daveau, Franck Letellier, Martine Hiron, Laurent Drouot, Maryvonne Daveau, Jean‐Philippe Salier – 20 September 2005 – Given the unknown timing of the onset of an acute systemic inflammation in humans, the fine tuning of cascades and pathways involved in the associated hepatocyte response cannot be appraised in vivo. Therefore, the authors used a genome‐wide and kinetic analysis in the human Hep3B hepatoma cell line challenged with a conditioned medium from bacterial lipopolysaccharide‐stimulated macrophages.

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