Cytokines increase CRE binding but decrease CRE‐mediated reporter activity in rat hepatocytes by increasing c‐Jun

Baochun Zhang, Shubing Liu, Michele D. Perpetua, William H. Walker, Brian G. Harbrecht – 26 April 2004 – The cyclic AMP response element (CRE) has been implicated in the regulation of the expression of many genes and cellular processes important in hepatocyte function. CRE sites exist in the promoter regions of several genes expressed during inflammation. Numerous studies on the role of CRE in hepatocyte gene expression have been performed in resting hepatocytes, but the role of CRE during inflammation is unknown.

Liver NK cells expressing TRAIL are toxic against self hepatocytes in mice

Makoto Ochi, Hideki Ohdan, Hiroshi Mitsuta, Takashi Onoe, Daisuke Tokita, Hidetaka Hara, Kohei Ishiyama, Wendy Zhou, Yuka Tanaka, Toshimasa Asahara – 26 April 2004 – Although it is known that activation of natural killer (NK) cells causes liver injury, the mechanisms underlying NK cell‐induced killing of self‐hepatocytes are not clear. We demonstrated that liver NK cells have cytotoxicity against normal syngeneic hepatocytes in mice. Polyinosinic‐polycytidylic acid (poly I:C) treatment enhanced hepatocyte toxicity of liver NK cells but not that of spleen NK cells.

Recently primed CD8+ T cells entering the liver induce hepatocytes to interact with naïve CD8+ T cells in the mouse

Nektarios Dikopoulos, Ursula Wegenka, Andrea Kröger, Hansjörg Hauser, Reinhold Schirmbeck, Jörg Reimann – 26 April 2004 – Large number of T cells traffic through the liver. In order to examine the effects of such traffic on the phenotype of hepatocytes, we vaccinated mice using DNA vaccines encoding antigens with MHC class I‐binding epitopes. Small numbers of activated CD8+ T blasts (105–106/liver) changed the surface phenotype and cytokine expression profile of hepatocytes (HCs).

Down‐regulation of the organic cation transporter 1 of rat liver in obstructive cholestasis

Gerald U. Denk, Carol J. Soroka, Albert Mennone, Hermann Koepsell, Ulrich Beuers, James L. Boyer – 26 April 2004 – The liver plays a major role in biotransformation and elimination of various therapeutic agents and xenobiotics, many of which are organic cations and substrates of the organic cation transporter 1 (Oct1, Slc22a1). Oct1 is expressed at the basolateral membranes of hepatocytes and proximal renal tubules. Although Oct1 is the major uptake mechanism in hepatocytes for many pharmaceutical compounds, little is known about the effects of liver injury on this process.

Low membrane protein sulfhydrils but not G6PD deficiency predict ribavirin‐induced hemolysis in hepatitis C

Ignazio Grattagliano, Stefan Russmann, Vincenzo O. Palmieri, Peter Jüni, Florian Bihl, Piero Portincasa, Giuseppe Palasciano, Bernhard H. Lauterburg – 26 April 2004 – Hemolysis is a frequent adverse effect of ribavirin (RBV). It has been suggested that oxidative stress plays a role, but mechanisms and predictive risk factors for severe forms remain unknown.

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