Title :

DHA-derived oxylipins, neuroprostanes and protectins, differentially and dose-dependently modulate the inflammatory response in human macrophages: putative mechanisms through PPAR activation

Author(s) :

Bosviel, Rémy [Auteur]
Unité de Nutrition Humaine [UNH]
Joumard-Cubizolles, Laurie [Auteur]
Unité de Nutrition Humaine [UNH]
Chinetti-Gbaguidi, Giulia [Auteur]

Université de Nice Sophia-Antipolis [UNSA]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Bayle, Dominique [Auteur]
Unité de Nutrition Humaine [UNH]
Copin, Corinne [Auteur]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Hennuyer, Nathalie [Auteur]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Duplan, Isabelle [Auteur]
Institut Pasteur de Lille
Institut National de la Santé et de la Recherche Médicale [INSERM]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Staels, Bart [Auteur]
Institut National de la Santé et de la Recherche Médicale [INSERM]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Zanoni, Giuseppe [Auteur]

Porta, Alessio [Auteur]

Balas, Laurence [Auteur]
Université de Montpellier [UM]

Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] [IBMM]
Galano, Jean-Marie [Auteur]
Université de Montpellier [UM]

Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] [IBMM]
Oger, Camille [Auteur]
Université de Montpellier [UM]

Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] [IBMM]
Mazur, André [Auteur]
Unité de Nutrition Humaine [UNH]
Durand, Thierry [Auteur]
Université de Montpellier [UM]

Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] [IBMM]
Gladine, Cécile [Auteur correspondant]
Unité de Nutrition Humaine [UNH]

Journal title :

Free Radical Biology and Medicine

Pages :

146-154

Publisher :

Elsevier

Publication date :

2017

ISSN :

0891-5849

Keyword(s) :

acide gras oméga 3
oxylipine
macrophage humain
activité anti-inflammatoire

English keyword(s) :

DHA
Free-radical mediated oxygenation
Inflammation
Lipid mediators
Neuroprostanes
Omega 3 PUFAs
PPARs
Oxylipins
Protectins

HAL domain(s) :

Sciences du Vivant [q-bio]/Alimentation et Nutrition
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Endocrinologie et métabolisme
Sciences du Vivant [q-bio]/Biotechnologies

English abstract : [en]

Whereas the anti-inflammatory properties and mechanisms of action of long chain. 3 PUFAs have been abundantly investigated, research gaps remain regarding the respective contribution and mechanisms of action of their ...
Show more >Whereas the anti-inflammatory properties and mechanisms of action of long chain. 3 PUFAs have been abundantly investigated, research gaps remain regarding the respective contribution and mechanisms of action of their oxygenated metabolites collectively known as oxylipins. A dose-dependent and comparative study was conducted using human primary macrophages. The aim was to compare the anti-inflammatory activity of two types of DHA- derived oxylipins including protectins (NPD1 and PDX), formed through lipoxygenase pathway and the neuroprostanes (14-A4t- and 4-F4t-NeuroP) formed through free-radical mediated oxygenation and suspected to be new anti-inflammatory mediators. Considering the potential ability of these lipid mediators to bind PPARs and knowing the central role of PPARs in the regulation of macrophage inflammatory response, transactivation assays was performed to compare the ability of protectins and neuroprostanes to activate PPARs. All molecules significantly reduced LPS-stimulated expression of cytokines but not at the same doses. Notably, NPD1 showed the most effect at 0.1 µM (IL-6:-14.9%, p<0.05 and TNF-α:-26.7%, p<0.05) while the other oxylipins had greater effects at 10 µM, with the strongest result obtained with the cyclopentenone neuroprostane 14-A4t-NeuroP (IL-6:-49.8%, p<0.001 and TNF-α:-40.8%, p<0.001, respectively). Concerning their binding to PPARs, Neuroprostanes and notably 14-A4t-NeuroP preferentially activate PPARγ while Protectins, especially PDX mainly activate PPARα. Combined together, these results bring new insights to the understanding of the role and mechanisms of action of DHA-derived oxylipins in the regulation of the macrophage inflammatory responseShow less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Non spécifiée

Popular science :

Non

Comment :

The authors would like to thank Severine Valero for her help in realizing ELISAs for this studyFunding: This work was supported by intramural funding from INRA - Human nutrition department and the French Research on Lipids & Nutrition Group (GLN)

Collections :

• Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (EGID) - U1011

Source :

Harvested from HAL