Biochemical and Biophysical Research Communications
Interleukin-6 regulates hepatic transporters during acute-phase response
Section snippets
Materials and methods
Cytokines and reagents. Recombinant human IL-6 with a specific activity of 5 × 106 B-cell stimulatory factor 2 U/mg protein was produced in the Escherichia coli expression system, purified to homogeneity by gel filtration and ion exchange high-performance liquid chromatography as described [21]. Endotoxin content was less than 3.5 pg/mg as measured in the Limulus assay, which is far below the concentration of LPS needed to induce an acute-phase protein production [22]. Steam distilled turpentine
Transporter mRNA expression in IL-6-treated wild-type mice
To determine whether an inflammatory response induced by IL-6 affects the mRNA expression of hepatobiliary organic anion transporters in wild-type mice in vivo, we quantified the steady-state mRNA levels of transport proteins exclusively localized either at the basolateral (Ntcp, Oatp1, and Mrp3) or canalicular (Bsep, Mrp2) plasma membrane of hepatocytes by Northern blotting (Figs. 1A and B). There was a reduction in the mRNA levels of all basolateral transporters analyzed: Ntcp mRNA declined
Discussion
The acute-phase reaction is an orchestrated complex response to tissue injury, infection or inflammation leading either to the induction of acute-phase proteins involved in the restoration of homeostasis (positive acute-phase proteins) or down-regulation of acute-phase proteins not required for host defense (negative acute-phase proteins) [3], [26]. Cytokines, particularly interleukin-6, are important mediators of the acute-phase response [2], [3]. However, the patterns of cytokine production
Acknowledgments
The authors thank Sonja Strauch, Petra Schmitz, Aline Müller, Sabine Beutelspacher, and Claudia Thomsa for their excellent technical assistance and H. Bluethmann (Roche, Basel/Switzerland) for providing BL/6 wild-type and homozygous IL-6 knock-out mice. Grant support: Sonderforschungsbereich 542 der Deutschen Forschungsgemeinschaft, Project C1 (2nd period) to C.G., A.G., and S.M.; Grants DFG SI 633/3-1 to E.S., DI 729/3-1 to C.G.D., and LA 997/3-1 to F.L.
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