ORBi: Bureau Fabrice - A proinflammatory role for the cyclopentenone prostaglandins at low micromolar concentrations: Oxidative stress-induced extracellular signal-regulated kinase activation without NF-kappa B inhibition

Reference : A proinflammatory role for the cyclopentenone prostaglandins at low micromolar concentra...


	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology Life sciences : Anatomy (cytology, histology, embryology...) & physiology Life sciences : Veterinary medicine & animal health
	To cite this reference:	http://hdl.handle.net/2268/8122

Title :	A proinflammatory role for the cyclopentenone prostaglandins at low micromolar concentrations: Oxidative stress-induced extracellular signal-regulated kinase activation without NF-kappa B inhibition
Language :	English
Author, co-author :	Bureau, Fabrice [Université de Liège - ULg > Département de sciences fonctionnelles > Biochimie et biologie moléculaire >]
	Desmet, Christophe [Université de Liège - ULg > > Biochimie et biologie moléculaire >]
	Burin Kefer, D. [ > > ]
	Jaspar, F. [ > > ]
	VolantI, C. [ > > ]
	Vanderplasschen, Alain [Université de Liège - ULg > > Immunologie et vaccinologie >]
	Pastoret, Paul-Pierre [Université de Liège - ULg > Département des maladies infectieuses et parasitaires > Département des maladies infectieuses et parasitaires >]
	PiettE, J. [ > > ]
	Lekeux, Pierre [Université de Liège - ULg > Département de sciences fonctionnelles > Physiologie >]
Publication date :	May-2002
Journal title :	Journal of Immunology
Publisher :	American Association of Immunologists
Volume :	168
Issue/season :	10
Pages :	5318-5325
Audience :	International
ISSN :	0022-1767
e-ISSN :	1550-6606
City :	Baltimore
Country :	MD
Abstract :	[en] An anti-inflammatory role and therapeutic potential for cyclopentenone PGs (cyPGs) has been suggested, based on observations that levels of cyPGs in exudates increase during the resolution phase of inflammation, and that exogenous cyPGs may attenuate the inflammatory response in vivo and in vitro mainly through inhibition of NF-kappaB, a critical activator of inflammatory gene expression. However, exogenous cyPGs inhibit NF-kappaB only at concentrations substantially higher than those of endogenous cyPGs present in inflammatory fluids, thus challenging the hypothesis that cyPGs are naturally occurring inhibitors of inflammation and suggesting that cyPGs at low concentrations might have previously unappreciated effects. In this study, using various cell types, we report that cyPGs, when used at concentrations substantially lower than required for NF-kappaB inhibition (viz, low micromolar concentrations), significantly potentiate the inflammatory response to TNF-alpha. At these concentrations, cyPGs induce production of reactive oxygen species, thereby synergizing with TNF-alpha to activate the extracellular signal-regulated kinase 1/2, an activation which in turn potentiates proinflammatory cytokine expression at both transcriptional and posttranscriptional levels. Our studs establishes a proinflammatory role for cyPGs at low micromolar concentrations, raises the possibility that cyPGs do not act as physiologic anti-inflammatory mediators, and questions the therapeutic potential of these compounds.
Target :	Researchers ; Professionals ; Students
Permalink :	http://hdl.handle.net/2268/8122

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