15-Deoxy-Δ12,14-prostaglandin J2 induces heme oxygenase-1 gene expression in a reactive oxygen species-dependent manner in human lymphocytes
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Title: | 15-Deoxy-Δ12,14-prostaglandin J2 induces heme oxygenase-1 gene expression in a reactive oxygen species-dependent manner in human lymphocytes |
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Authors: | Álvarez Maqueda, Moisés | El Bekay, Rajaa | Alba Jiménez, Gonzalo | Monteseirín Mateo, Javier | Chacón Fernández, Pedro | Vega Rioja, Antonio | Martín-Nieto, José | Bedoya Bergua, Francisco Javier | Pintado Sanjuan, Elizabeth | Sobrino Beneyto, Francisco |
Research Group/s: | Genética Humana y de Mamíferos |
Center, Department or Service: | Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología | Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular | Hospital Universitario Virgen Macarena. Servicio de Inmunología y Alergia |
Keywords: | 15-Deoxy-Δ12,14-prostaglandin J2 | Heme oxygenase-1 | Gene expression | Reactive oxygen species | Human lymphocytes |
Knowledge Area: | Genética | Bioquímica y Biología Molecular |
Date Created: | 16-Jan-2004 |
Issue Date: | 21-May-2004 |
Publisher: | American Society for Biochemistry and Molecular Biology |
Citation: | ÁLVAREZ MAQUEDA, Moisés, et al. "15-Deoxy-Δ12,14-prostaglandin J2 induces heme oxygenase-1 gene expression in a reactive oxygen species-dependent manner in human lymphocytes". Journal of Biological Chemistry. Vol. 279, No. 21 (May 2004). ISSN 0021-9258, pp. 21929-21937 |
Abstract: | 15-Deoxy-Δ12,14-prostaglandin J2 (15dPGJ2) has been recently proposed as a potent anti-inflammatory agent. However, the mechanisms by which 15dPGJ2 mediates its therapeutic effects in vivo are unclear. We demonstrate that 15dPGJ2 at micromolar (2.5–10 µM) concentrations induces the expression of heme oxygenase-1 (HO-1), an anti-inflammatory enzyme, at both mRNA and protein levels in human lymphocytes. In contrast, troglitazone and ciglitazone, two thiazolidinediones that mimic several effects of 15dPGJ2 through their binding to the peroxisome proliferator-activated receptor (PPAR)-γ, did not affect HO-1 expression, and the positive effect of 15dPGJ2 on this process was mimicked instead by other cyclopentenone prostaglandins (PG), such as PGD2 (the precursor of 15dPGJ2) and PGA1 and PGA2 which do not interact with PPAR-γ. Also, 15dPGJ2 enhanced the intracellular production of reactive oxygen species (ROS) and increased xanthine oxidase activity in vitro. Inhibition of intracellular ROS production by N-acetylcysteine, TEMPO, Me2SO, 1,10-phenanthroline, or allopurinol resulted in a decreased 15dPGJ2-dependent HO-1 expression in the cells. Furthermore, buthionine sulfoximine, an inhibitor of reduced glutathione synthesis, or Fe2+/Cu2+ ions enhanced the positive effect of 15dPGJ2 on HO-1 expression. On the other hand, the inhibition of phosphatidylinositol 3-kinase or p38 mitogen-activated protein kinase, or the blockade of transcription factor NF-κB activation, hindered 15dPGJ2-elicited HO-1 expression. Collectively, the present data suggest that 15dPGJ2 anti-inflammatory actions at pharmacological concentrations involve the induction of HO-1 gene expression through mechanisms independent of PPAR-γ activation and dependent on ROS produced via the xanthine/xanthine oxidase system and/or through Fenton reactions. Both phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase signaling pathways also appear implicated in modulation of HO-1 expression by 15dPGJ2. |
Sponsor: | This work was supported in part by Ministerio de Ciencia y Tecnología Grants SAF/2000-117 (to F. S.) and SAF/2000-161 (to F. J. B.) and by a grant from the Fundación SEIAC, Spain (to J. M.). |
URI: | http://hdl.handle.net/10045/9732 |
ISSN: | 0021-9258 (Print) | 1083-351X (Online) |
DOI: | 10.1074/jbc.M400492200 |
Language: | eng |
Type: | info:eu-repo/semantics/article |
Rights: | This research was originally published in Journal of Biological Chemistry. Álvarez Maqueda, Moisés, et al. 15-Deoxy-Δ12,14-prostaglandin J2 induces heme oxygenase-1 gene expression in a reactive oxygen species-dependent manner in human lymphocytes. Journal of Biological Chemistry. 2004. 279: 21929-21937. © the American Society for Biochemistry and Molecular Biology |
Peer Review: | si |
Appears in Collections: | INV - GHM - Artículos de Revistas |
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