| First Author | Siewert E | Year | 2004 |
| Journal | Biochem Biophys Res Commun | Volume | 322 |
| Issue | 1 | Pages | 232-8 |
| PubMed ID | 15313196 | Mgi Jnum | J:113760 |
| Mgi Id | MGI:3687619 | Doi | 10.1016/j.bbrc.2004.07.102 |
| Citation | Siewert E, et al. (2004) Interleukin-6 regulates hepatic transporters during acute-phase response. Biochem Biophys Res Commun 322(1):232-8 |
| abstractText | Cholestasis develops during inflammatory conditions characterized by the release of cytokines like interleukin-6 (IL-6), which is the major player in the hepatic acute-phase response. However, the exact contribution of IL-6 to transporter down-regulation is unclear. Therefore, we compared wild-type and IL-6-deficient mice after IL-6-injection and induction of an aseptic (turpentine-injection) or septic (LPS-injection) acute-phase response. Down-regulation of basolateral (Ntcp, Oatp1, and Mrp3) and canalicular (Mrp2, Bsep) transporter mRNA occurred after treatment with IL-6, turpentine, and LPS. In IL-6-deficient mice, turpentine failed to decrease mRNA-levels of basolateral and canalicular transporters, whereas LPS-mediated down-regulation of Ntcp, Mrp3, and Mrp2 was abolished at later time points (24 h). In conclusion, induction of an aseptic and septic acute-phase response leads to the down-regulation of basolateral and canalicular organic anion transporters. IL-6 is required for transporter down-regulation during aseptic inflammation. Furthermore, IL-6 also contributes to transporter regulation during LPS-induced cholestasis at more delayed time points. |
