+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Interleukin-6 regulates hepatic transporters during acute-phase response



Interleukin-6 regulates hepatic transporters during acute-phase response



Biochemical and Biophysical Research Communications 322(1): 232-238



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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 012227884

Download citation: RISBibTeXText

PMID: 15313196

DOI: 10.1016/j.bbrc.2004.07.102


Related references

Histamine regulates the expression of interleukin-6, IL-6 receptor and IL-6 related hepatic acute phase proteins. 9TH INTERNATIONAL CONGRESS OF IMMUNOLOGY [Author] The 9th International Congress of Immunology : 208, 1995

Interleukin-6 Its hepatic receptor and the acute-phase response of the liver. European Surgical Research 24(5): 319, 1992

Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. Proceedings of the National Academy of Sciences of the United States of America 102(19): 6843-6848, 2005

Tumor necrosis factor, interleukin 6, and the acute phase response following hepatic ischemia/reperfusion. Journal of Surgical Research 55(1): 49-54, 1993

Increased serum interleukin-6 level and reduction of hepatic acute-phase response after major hepatectomy. European Surgical Research. Europaische Chirurgische Forschung. Recherches Chirurgicales Europeennes 28(2): 96, 1996

Increased Serum Interleukin-6 Level and Reduction of Hepatic Acute-Phase Response after Major Hepatectomy. European Surgical Research 28(2): 96-103, 1996

Elevated circulating interleukin-6 is associated with an acute-phase response but reduced fixed hepatic protein synthesis in patients with cancer. Annals of Surgery 213(1): 26-31, 1991

Effect of interleukin-2 on peripheral blood mononuclear cell cytokine production and the hepatic acute phase protein response. Clinical Immunology (Orlando) 104(2): 174-182, 2002

Acute-phase reaction induces a specific complex between hepatic nuclear proteins and the interleukin 6 response element of the rat a2-macroglobulin gene. Proceedings of the National Academy of Sciences of the United States of America 87(6): 64-8, 1990

Liver nonparenchymal cells are stimulated to provide interleukin 6 for induction of the hepatic acute-phase response in endotoxemia but not in remote localized inflammation. Archives of Surgery 127(1): 31-6; Discussion 36-7, 1992

Acute-phase reaction induces a specific complex between hepatic nuclear proteins and the interleukin 6 response element of the rat alpha 2-macroglobulin gene. Proceedings of the National Academy of Sciences of the United States of America 87(6): 2364-2368, 1990

Peripheral blood cells from weight-losing cancer patients control the hepatic acute phase response by a primarily interleukin-6 dependent mechanism. International Journal of Oncology 15(4): 823-827, 1999

Increased fibrinogen synthesis in mice during the acute phase response: Co-operative interaction of interleukin 1, interleukin 6, and interleukin 1 receptor antagonist. Cytokine 5(5): 454-458, 1993

Interleukin-1 receptor antagonist induction as an additional mechanism for liver receptor homolog-1 to negatively regulate the hepatic acute phase response. Journal of Biological Chemistry 282(7): 4393-4399, 2007

Acute-phase response factor, a nuclear factor binding to acute-phase response elements, is rapidly activated by interleukin-6 at the posttranslational level. Molecular and Cellular Biology 13(1): 276-288, 1993