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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 >

5'-methylthioadenosine modulates the inflammatory response to endotoxin in mice and in rat hepatocytes
Authors: Hevia, H. (Henar)
Varela-Rey, M. (Marta)
Corrales, F.J. (Fernando José)
Berasain, C. (Carmen)
Martinez-Chantar, M.L. (María Luz)
Latasa, M.U. (María Ujué)
Lu, S.C. (Shelly C.)
Mato, J.M. (José María)
Ruiz Garcia-Trevijano, E. (Elena)
Avila, M.A. (Matías Antonio)
Keywords: Anti-Inflammatory Agents/pharmacology
Deoxyadenosines/pharmacokinetics
Hepatocytes/drug effects
Hepatocytes/immunology
Lipopolysaccharides/pharmacology
Shock, Septic/drug therapy
Thionucleosides/pharmacokinetics
Issue Date: 2004
Publisher: Wiley-Blackwell
Publisher version: http://bit.ly/Hray3K
ISSN: 1527-3350
Citation: Hevia H, Varela-Rey M, Corrales FJ, Berasain C, Martinez-Chantar ML, Latasa MU, et al. 5'-Methylthioadenosine Modulates the Inflammatory Response to Endotoxin in Mice and in Rat Hepatocytes. Hepatology 2004 Apr;39(4):1088-1098.
Abstract
5'-methylthioadenosine (MTA) is a nucleoside generated from S-adenosylmethionine (AdoMet) during polyamine synthesis. Recent evidence indicates that AdoMet modulates in vivo the production of inflammatory mediators. We have evaluated the anti-inflammatory properties of MTA in bacterial lipopolysaccharide (LPS) challenged mice, murine macrophage RAW 264.7 cells, and isolated rat hepatocytes treated with pro-inflammatory cytokines. MTA administration completely prevented LPS-induced lethality. The life-sparing effect of MTA was accompanied by the suppression of circulating tumor necrosis factor-alpha (TNF-alpha), inducible NO synthase (iNOS) expression, and by the stimulation of IL-10 synthesis. These responses to MTA were also observed in LPS-treated RAW 264.7 cells. MTA prevented the transcriptional activation of iNOS by pro-inflammatory cytokines in isolated hepatocytes, and the induction of cyclooxygenase 2 (COX2) in RAW 264.7 cells. MTA inhibited the activation of p38 mitogen-activated protein kinase (MAPK), c-jun phosphorylation, inhibitor kappa B alpha (IkappaBalpha) degradation, and nuclear factor kappaB (NFkappaB) activation, all of which are signaling pathways related to the generation of inflammatory mediators. These effects were independent of the metabolic conversion of MTA into AdoMet and the potential interaction of MTA with the cAMP signaling pathway, central to the anti-inflammatory actions of its structural analog adenosine. In conclusion, these observations demonstrate novel immunomodulatory properties for MTA that may be of value in the management of inflammatory diseases.
Permanent link: http://hdl.handle.net/10171/21487
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Oncobiología - Artículos de revista
DA - CIMA - Unidad de Proteómica, Genómica y Bioinformática - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Hepatología bioquímica - Artículos de revista

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