Impact of interleukin-6 classic- and trans-signaling on liver damage and regeneration.
Interleukin-6 (IL-6) has been suggested to play a pivotal role in liver regeneration. IL-6 on target cells activates a receptor complex consisting of the IL-6 receptor (IL-6R) and the signal transducing receptor subunit gp130. Not all cells in the body express the IL-6R on the cell surface. IL-6 can signal via two different pathways: classical signaling via the membrane bound IL-6R and IL-6 trans-signaling via a naturally occurring soluble IL-6R (sIL-6R). This second pathway widens the scope of IL-6 signaling since also cells expressing no membrane bound IL-6R can be stimulated by the trans-signal pathway. Mimicking IL-6 trans-signaling via a designer molecule, Hyper-IL-6 has been shown to accelerate liver regeneration. Another designer molecule, sgp130Fc, specifically blocks IL-6 trans-signaling. Using these proteins we investigated the contribution of IL-6 classic- and trans-signaling in the liver. Here we review the role of IL-6 signaling in response to liver damage and during liver regeneration.
Drucker
Claudia
C
Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Gewiese
Jessica
J
Malchow
Sven
S
Scheller
Jürgen
J
Rose-John
Stefan
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D017209:Apoptosis / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D050822:Cytokine Receptor gp130 / Q000276:immunology / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008115:Liver Regeneration / Q000276:immunology; D019947:Receptors, Interleukin-6 / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130; C502936:tocilizumab