Combined interleukin 6 and soluble interleukin 6 receptor accelerates murine liver regeneration
M Peters, G Blinn, T Jostock, P Schirmacher… - Gastroenterology, 2000 - Elsevier
M Peters, G Blinn, T Jostock, P Schirmacher, KHM Zum Büschenfelde, PR Galle…
Gastroenterology, 2000•ElsevierBackground & Aims: Liver regeneration after loss of hepatic tissue leads to hepatocyte and
nonparenchymal cell proliferation and rapid restoration of liver parenchyma. Interleukin (IL)-
6 is a key inducer of transcription factors involved in liver regeneration. Whenever IL-6
activates target cells, it binds to a specific IL-6 receptor (IL-6R). The IL-6/IL-6R complex then
associates with the signal transducer gp130, leading to activation of intracellular signaling.
Methods: We have recently constructed the designer cytokine Hyper-IL-6 consisting of …
nonparenchymal cell proliferation and rapid restoration of liver parenchyma. Interleukin (IL)-
6 is a key inducer of transcription factors involved in liver regeneration. Whenever IL-6
activates target cells, it binds to a specific IL-6 receptor (IL-6R). The IL-6/IL-6R complex then
associates with the signal transducer gp130, leading to activation of intracellular signaling.
Methods: We have recently constructed the designer cytokine Hyper-IL-6 consisting of …
Background & Aims
Liver regeneration after loss of hepatic tissue leads to hepatocyte and nonparenchymal cell proliferation and rapid restoration of liver parenchyma. Interleukin (IL)-6 is a key inducer of transcription factors involved in liver regeneration. Whenever IL-6 activates target cells, it binds to a specific IL-6 receptor (IL-6R). The IL-6/IL-6R complex then associates with the signal transducer gp130, leading to activation of intracellular signaling.
Methods
We have recently constructed the designer cytokine Hyper-IL-6 consisting of soluble IL-6R covalently linked to IL-6, which directly stimulates gp130 even in the absence of membrane-bound IL-6R. We compared the influence of IL-6 and Hyper-IL-6 on liver regeneration after partial hepatectomy in mice.
Results
The IL-6/soluble IL-6 fusion protein Hyper-IL-6, but not IL-6 alone, led to an earlier onset of hepatocellular proliferation resulting in an acceleration of liver weight restoration. Also, during liver regeneration, soluble IL-6R levels were increased.
Conclusions
These results emphasize a central role for IL-6 and soluble IL-6R in liver regeneration and indicate a possible therapeutic potential for the designer cytokine Hyper-IL-6 in clinical situations associated with liver regeneration such as acute hepatic failure or resection of chronically damaged liver tissue.
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