PeproTech Inc.
Originally published online as doi:10.1189/jlb.0705411 on April 19, 2006

Published online before print April 19, 2006
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jlb.0705411v1
80/1/152    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vega, A.
Right arrow Articles by Sobrino, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vega, A.
Right arrow Articles by Sobrino, F.
(Journal of Leukocyte Biology. 2006;80:152-163.)
© 2006 by Society for Leukocyte Biology

Modulation of IgE-dependent COX-2 gene expression by reactive oxygen species in human neutrophils

Antonio Vega*,{dagger}, Pedro Chacón*,{dagger}, Gonzalo Alba*, Rajaa El Bekay*,{ddagger}, Javier Monteseirín*,{ddagger}, José Martín-Nieto§ and Francisco Sobrino*,1

* Departamento de Bioquímica Médica y Biología Molecular, Universidad de Sevilla, Sevilla, Spain;
{dagger} Servicio de Inmunología y Alergia, Hospital Universitario Virgen Macarena, Sevilla, Spain;
{ddagger} Clínica Sagrado Corazón, Sevilla, Spain; and
§ Departamento de Fisiología, Genética y Microbiología, Universidad de Alicante, Alicante, Spain

1 Correspondence: Dpto. Bioquímica Médica y Biología Molecular, Facultad de Medicina, Universidad de Sevilla, E-41009 Sevilla, Spain. E-mail: fsobrino{at}us.es

Cyclooxygenase (COX) is a key enzyme in prostaglandin (PG) synthesis. Up-regulation of its COX-2 isoform is responsible for the increased PG release, taking place under inflammatory conditions, and also, is thought to be involved in allergic and inflammatory diseases. In the present work, we demonstrate that COX-2 expression becomes highly induced by anti-immunoglobulin E (IgE) antibodies and by antigens in human neutrophils from allergic patients. This induction was detected at mRNA and protein levels and was accompanied by a concomitant PGE2 and thromboxane A2 release. We also show evidence that inhibitors of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, such as 4-(2-aminoethyl)benzenesulphonyl fluoride and 4-hydroxy-3-methoxyaceto-phenone, completely cancelled anti-IgE-induced COX-2 protein up-regulation, suggesting that this process is mediated by reactive oxygen species (ROS) derived from NADPH oxidase activity. Moreover, the mitogen-activated protein kinases (MAPKs), p38 and extracellular signal-regulated kinase, and also, the transcription factor, nuclear factor (NF)-{kappa}B, are involved in the up-regulation of COX-2 expression, as specific chemical inhibitors of these two kinases, such as SB203580 and PD098059, and of the NF-{kappa}B pathway, such as N({alpha})-benzyloxycarbonyl-l-leucyl-l-leucyl-l-leucinal, abolished IgE-dependent COX-2 induction. Evidence is also presented, using Fe2+/Cu2+ ions, that hydroxyl radicals generated from hydrogen peroxide through Fenton reactions could constitute candidate modulators able to directly trigger anti-IgE-elicited COX-2 expression through MAPK and NF-{kappa}B pathways. Present results underscore a new role for ROS as second messengers in the modulation of COX-2 expression by human neutrophils in allergic conditions.

Key Words: prostaglandins • allergy • signal transduction • ROS




This article has been cited by other articles:


Home page
 J. Cell Sci.Home page
A. Vega, P. Chacon, J. Monteseirin, R. El Bekay, G. Alba, J. Martin-Nieto, and F. Sobrino
Expression of the transcription factor NFAT2 in human neutrophils: IgE-dependent, Ca2+- and calcineurin-mediated NFAT2 activation
J. Cell Sci., July 15, 2007; 120(14): 2328 - 2337.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
F.-Y. Lin, Y.-H. Chen, J.-S. Tasi, J.-W. Chen, T.-L. Yang, H.-J. Wang, C.-Y. Li, Y.-L. Chen, and S.-J. Lin
Endotoxin Induces Toll-Like Receptor 4 Expression in Vascular Smooth Muscle Cells via NADPH Oxidase Activation and Mitogen-Activated Protein Kinase Signaling Pathways
Arterioscler. Thromb. Vasc. Biol., December 1, 2006; 26(12): 2630 - 2637.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Hatziapostolou, C. Polytarchou, P. Katsoris, J. Courty, and E. Papadimitriou
Heparin Affin Regulatory Peptide/Pleiotrophin Mediates Fibroblast Growth Factor 2 Stimulatory Effects on Human Prostate Cancer Cells
J. Biol. Chem., October 27, 2006; 281(43): 32217 - 32226.
[Abstract] [Full Text] [PDF]