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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Hepatología bioquímica > DA - CIMA - Terapia génica y Hepatología - Hepatología bioquímica - Artículos de revista >

Anti-inflammatory effects of hepatocyte growth factor: induction of interleukin-1 receptor antagonist
Authors: Molnar, C. (Clemens)
Garcia-Trevijano, E.R. (Elena R.)
Ludwiczek, O. (Othmar)
Talabot, D. (Dominique)
Kaser, A. (Arthur)
Mato, J.M. (José María)
Fritsche, G. (Gernot)
Weiss, G. (Günter)
Gabay, C. (Cem)
Avila, M.A. (Matías Antonio)
Tilg, H. (Herbert)
Keywords: HGF
Hepatocytes
HepG2
Monocytes
IL-1Ra
Issue Date: 2004
Publisher: John Libbey Eurotext
Publisher version: http://www.jle.com/en/revues/bio_rech/ecn/e-docs/00/04/08/31/resume.phtml
ISSN: 1148-5493
Citation: Molnar C, Garcia-Trevijano ER, Ludwiczek O, Talabot D, Kaser A, Mato JM, et al. Anti-inflammatory effects of hepatocyte growth factor: induction of interleukin-1 receptor antagonist. Eur Cytokine Netw 2004 Oct-Dec;15(4):303-311.
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-1beta (IL-1beta) 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-1beta 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-1beta 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-alpha (TNF-alpha) 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.
Permanent link: http://hdl.handle.net/10171/23250
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Hepatología bioquímica - Artículos de revista

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