Interleukin-6 plays a crucial role in the hepatic expression of SOCS3 during acute inflammatory processes in vivo.
OBJECTIVE
Interleukin-6 is mandatory for liver regeneration after injury and for the hepatic expression of acute phase proteins and cytochrome P450 enzymes during inflammation. Due to its crucial contribution to the maintenance of homeostasis IL-6 signaling is tightly controlled. Suppressor of cytokine signaling (SOCS) 3 is a potent IL-6-induced feedback inhibitor terminating IL-6 signal transduction. However, several signaling pathways converge on SOCS3: SOCS3 can be induced by other mediators in vitro, and it does not exclusively inhibit IL-6 signaling. The individual contribution of each cytokine to the induction of SOCS3 in vivo is unknown.


METHODS
Using IL-6-deficient mice we analyzed the role of interleukin-6 for the hepatic SOCS3 expression in response to turpentine and LPS as models of aseptic and bacterial inflammation, respectively.


RESULTS
In wild-type animals, turpentine and LPS elicited strong induction of SOCS3. IL-6-deficient mice, by contrast, showed severely impaired SOCS3 expression in response to both stimuli: turpentine failed to induce SOCS3 mRNA; in LPS-induced inflammation, the early inductive response 60min after LPS injection was absent, and the delayed expression of SOCS3 was markedly reduced. The residual delayed SOCS3 expression in IL-6-deficient mice was abolished in IL-6/TNFR-1 knockout mice.


CONCLUSIONS
Our data strongly argue for a crucial role of IL-6 in the hepatic expression of SOCS3 during acute inflammatory processes in vivo. Although other cytokines are capable of inducing SOCS3 their contribution seems to be minor.
Yang
Xiang-Ping
XP
Department of Biochemistry, Medical School, RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
Schaper
Fred
F
Teubner
Andreas
A
Lammert
Frank
F
Heinrich
Peter C
PC
Matern
Siegfried
S
Siewert
Elmar
E
D000818:Animals; D017931:DNA Primers; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012486:Salmonella typhimurium / Q000276:immunology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*; D014425:Turpentine / Q000633:toxicity
D017931:DNA Primers; D015850:Interleukin-6; D008070:Lipopolysaccharides; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D012313:RNA; D014425:Turpentine