Interleukin-6 trans-signaling regulates glycogen consumption after D-galactosamine-induced liver damage.
The cytokine interleukin-6 (IL-6) is important for liver regeneration. IL-6 can stimulate target cells either by binding to the membrane-bound IL-6 receptor (IL-6R) leading to dimerization and activation of gp130 or by binding to a soluble IL-6R that results in an activation of gp130 independently of membrane-bound IL-6R, a process called trans-signaling. We have established a transgenic mouse line, in which only trans-signaling is abrogated whereas signaling via the membrane-bound IL-6R is intact. In the present study we employed this mouse model to ask whether the activity of IL-6 during repair of mild liver damage acts via classic or trans-signaling. We analyzed liver regeneration and showed that intracellular signaling, proliferation, and glycogenolysis are reduced in the transgenic mice and thus are regulated by IL-6 trans-signaling. Taken together our results show that upon liver damage, activation of the gp130 pathway depends on the sIL-6R.
Drucker
Claudia
C
Institute of Biochemistry, Christian-Albrechts-University of Kiel, Olshausenstrasse 40, Kiel, Germany.
Rabe
Björn
B
Chalaris
Athena
A
Schulz
Elsbeth
E
Scheller
Jürgen
J
Rose-John
Stefan
S
D000818:Animals; D050822:Cytokine Receptor gp130 / Q000378:metabolism*; D005688:Galactosamine / Q000008:administration & dosage; D006003:Glycogen / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017114:Liver Failure, Acute / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008115:Liver Regeneration / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
C494199:IL6ST protein, human; D015850:Interleukin-6; D011993:Recombinant Fusion Proteins; D050822:Cytokine Receptor gp130; D005688:Galactosamine; D006003:Glycogen; C519852:olamkicept