@Article{,
AUTHOR = {Clemens Molnar, Elena R. Garcia-Trevijano, Othmar Ludwiczek, Dominique Talabot, Arthur Kaser, Jose M. Mato, Gernot Fritsche, Günter Weiss, Cem Gabay, Matias A. Avila, Herbert Tilg},
TITLE = {Anti-inflammatory effects of hepatocyte growth factor: induction of interleukin-1 receptor antagonist},
JOURNAL = {European Cytokine Network},
VOLUME = {15},
YEAR = {2004},
NUMBER = {4},
PAGES = {303--311},
URL = {http://www.techscience.com/ECN/v15n4/66360},
ISSN = {1952-4005},
ABSTRACT = {Hepatocyte growth factor (HGF) prevents liver failure in various animal models including
endotoxin-induced acute liver failure. We were interested to find out whether human HGF exerts anti-inflammatory
effects by modulation of cytokine synthesis. Therefore, human HepG2 cells were cultured with
increasing concentrations of HGF. HGF dose-dependently upregulated the production of interleukin-1 receptor
antagonist (IL-1Ra). Incubation of HepG2 cells with interleukin-1β (IL-1β) caused an increase in IL-1Ra levels,
while interleukin-6 (IL-6) had no effect on IL-1Ra synthesis. Co-stimulation of HepG2 cells with HGF + IL-1β
resulted in a synergistic effect on IL-1Ra mRNA and protein expression. Stimulation of freshly isolated mouse
hepatocytes from male C57 BL/6 mice with HGF increased IL-1Ra mRNA and protein synthesis dose-dependently.
A co-stimulation with HGF and IL-1β had a synergistic effect on IL-1Ra mRNA expression but only
a partially additive effect on IL-1Ra protein synthesis. HGF-induced IL-1Ra production was significantly
decreased by the mitogen-activated protein kinase (MAPK) inhibitor PD98059. Accordingly, HGF stimulation
specifically increased MAPK-dependent signalling pathway (p42/44). In contrast, in preactivated PBMC mRNA
expression and protein synthesis of IL-1Ra, interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) were
unaffected after stimulation with HGF. In conclusion, our data suggest that HGF exerts anti-inflammatory effects
by modulating the signal transduction cascade leading to increased expression of IL-1Ra, which might explain the
protective and regenerative properties of this cytokine in animal models of liver failure.},
DOI = {}
}