Programme de R&D sur l’inflammation et sa rÉsolution
Ambiotis est la première CRO mondiale spécialiste du processus de résolution de l’inflammation
L’inflammation est une réponse naturelle de l’hôte à une blessure, une irritation ou une infection. Le processus se divise en 3 grandes étapes : l’initiation, l’amplification et la résolution.
Lorsqu’elle est correctement contrôlée, l’inflammation est supposée s’éteindre et permettre la restauration complète du tissu ou de l'organe ciblé.
De multiples types cellulaires et effecteurs biochimiques appartenant en particulier au système de l’immunité innée et adaptative sont impliqués et finement régulés au cours de ce processus.
L’extinction de signaux pro-inflammatoires n’est pas suffisante pour permettre le retour du tissu à son état initial.
Par exemple, les anti-inflammatoires non stéroidiens (Non Steroidal Anti Inflammatory Drugs (NSAIDs)) ont été conçus sur cette hypothèse : ils inhibent le processus inflammatoire en inhibant les cyclooxgénases et donc la synthèse de PGE2 . Bien que très efficaces contre les inflammations aigues, ils montrent une efficacité relative lors d’inflammations chroniques. De plus, de nombreux effets secondaires néfastes ont été rapportés.
La dernière décennie a permis de mettre au jour de nouvelles familles de molécules qui sont en réalité sécrétées de manière finement régulée tout au long de la réponse inflammatoire incluant la phase de résolution.
La résolution est en réalité un processus actif, impliquant des médiateurs spécifiques biologiquement actifs et qui peuvent êtres utilisés en tant que biomarqueurs de l’homéostasie.
Ces biomarqueurs sont issus du métabolisme des acides gras poly-insaturés (AGPI) oméga-3 et oméga-6 : ARA, DHA, EPA et DPA et sont appelés lipoxines, résolvines, marésines et protectines, collectivement regroupées sous le terme de SPMs (Specialized Pro-resolving Mediators)
Ces molécules contrôlent les mécanismes physiologiques impliqués dans la terminaison de l’inflammation depuis la décroissance du recrutement des cellules inflammatoires, l’élimination de pathogènes jusqu’à la cicatrisation et la diminution de la douleur. Cela amène ainsi des perspectives prometteuses pour le développement de nouveaux médicaments contre les maladies inflammatoires chroniques.
En effet, une nouvelle branche de la pharmacologie a récemment émergé : la pharmacologie de la résolution. A la différence de la pharmacologie de l’inflammation qui vise à bloquer les médiateurs responsables d’effets néfastes sur les tissus, la pharmacologie de la résolution cherche à activer, favoriser ou intensifier les processus cellulaires impliqués dans le retour à l’état initial (limiter/réparer les dommages, nettoyer le site inflammatoire des débris…).
« The mapping of new resolution circuits has opened the possibility for understanding mechanisms that lead from acute to chronic inflammation, or to the resolution thereof, as well as to potential, resolution-based immunopharmacological therapies. »
(Serhan CN, Am J Pathol 2010)
« In the past decade, a new paradigm in our understanding of the inflammatory process has emerged with the appreciation of genetic, molecular, and cellular mechanisms that are engaged to actively resolve inflammation. The ‘resolution of acute inflammation’ is enabled by counter-regulatory checkpoints to terminate the inflammatory reaction, promoting healing and repair. It may be possible to harness this knowledge for innovative approaches to the treatment of inflammatory pathologies. Here we discuss current translational attempts to develop agonists at proresolving targets as a strategy to rectify chronic inflammatory status. We reason this new approach will lead to the identification of better drugs that will establish a new branch of pharmacology, ‘resolution pharmacology’ »
(Perretti M, Trends in Pharmacological Science,2015)
« it has been proposed that some diseases that are associated with chronic inflam mation may be underpinned by dysregulated resolution as much as driven by ongoing proinflammatory processes, and that therapy based on rectifying these defects will help to guide ongoing inflammation down a proresolution pathway. »
(Fullerton JM, Nature Rev Drug discovery, 2016)
Devenons partenaires : notre objectif est de faire de nos innovations votre futur
Depuis sa création, Ambiotis mène des programmes de R&D et investigue les mécanismes naturels impliqués dans la terminaison du processus inflammatoire de manière à pouvoir les favoriser à l’aide de nouvelles molécules.
La société a ainsi acquis une solide expérience et expertise de ce champ de manière à proposer des modèles finement caractérisés en étroite concomitance avec une approche analytique robuste.
Publications
Proteomic and Lipidomic Profiling of Calves Experimentally Co-Infected with Influenza D Virus and Mycoplasma bovis: Insights into the Host–Pathogen Interactions.
Ignacio Alvarez, , Mariette Ducatez, Yongzhi Guo, Adrien Lion, Anna Widgren, Marc Dubourdeau, Vincent Baillif, Laure Saias, Siamak Zohari, Jonas Bergquist, Gilles Meyer, Jean-Francois Valarcher and Sara Hägglund. Viruses. 2024 Feb
15-Lipoxygenase promotes resolution of inflammation in lymphedema by controlling Treg cell function through IFN-β.
. Nature Communications. 2024 Jan
Targeting inflammation and pro-resolving mediators with Anetholea anisita extract to improve scalp condition.
. Int J Cosmet Sci. 2022 Dec
DHA, RvD1, RvD5, and MaR1 reduce human coronary arteries contractions induced by PGE2.
Amel Bouhadoun, Hasanga D Manikpurage, Catherine Deschildre, Sara Zalghout, Marc Dubourdeau, Valérie Urbach, Benoît Ho-Tin-Noe, Lydia Deschamps, Jean-Baptiste Michel, Dan Longrois, Xavier Norel. Prostaglandins Other Lipid Mediat. 2022 Dec
CF Patients' Airway Epithelium and Sex Contribute to Biosynthesis Defects of Pro-Resolving Lipids.
Mickael Shum, Charlie M London, Maelle Briottet, Khadeeja Adam Sy, Vincent Baillif, Reginald Philippe, Abdolhossein Zare, Sadegh Ghorbani-Dalini, Natacha Remus, Agathe Tarze, Virginie Escabasse, Ralph Epaud, Marc Dubourdeau, Valerie Urbach. Front Immunol. 2022 Jun
Nicotinamide Mononucleotide Administration Triggers Macrophages Reprogramming and Alleviates Inflammation During Sepsis Induced by Experimental Peritonitis.
Cécile Cros, Marielle Margier, Hélène Cannelle, Julie Charmetant, Nicolas Hulo, Laurent Laganier, Alessia Grozio and Matthias Canault. Front. Mol. Biosci. 2022 Jun
The Natural Combination Medicine Traumeel (Tr14) Improves Resolution of Inflammation by Promoting the Biosynthesis of Specialized Pro-Resolving Mediators.
Paul M. Jordan, Emeline van Goethem, Andrea M. Müller, Kathrin Hemmer, Virginie Gavioli, Vincent Baillif, Yvonne Burmeister, Natascha Krömmelbein, Marc Dubourdeau, Bernd Seilheimer and Oliver Werz. Pharmaceuticals 2021 Nov
Agonist anti-ChemR23 mAb reduces tissue neutrophil accumulation and triggers chronic inflammation resolution.
C Trilleaud, V Gauttier, K Biteau, I Girault, L Belarif, C Mary, S Pengam, G Teppaz, V Thepenier, R Danger, G Robert-Siegwald, M Néel, S Bruneau, A Glémain, A Néel, A Poupon, J F Mosnier, G Chêne, M Dubourdeau, G Blancho, B Vanhove, N Poirier. Science Advances, 2021 Apr
The Atlas of Inflammation Resolution.
Charles N Serhan, Shailendra K Gupta, Mauro Perretti, Catherine Godson, Eoin Brennan, Yongsheng Li, Oliver Soehnlein, Takao Shimizu, Oliver Werz, Valerio Chiurchiù, Angelo Azzi, Marc Dubourdeau, Suchi Smita Gupta, Patrick Schopohl, Matti Hoch, Dragana Gjorgevikj, Faiz M Khan, David Brauer, Anurag Tripathi, Konstantin Cesnulevicius, David Lescheid, Myron Schultz, Eva Särndahl, Dirk Repsilber, Robert Kruse, Angelo Sala, Jesper Z Haeggström, Bruce D Levy, János G Filep, Olaf Wolkenhauer. Mol. Aspects Med., 2020 Aug
Resolvin D1 reduces lung infection and inflammation activating resolution in cystic fibrosis.
Domenico Mattoscio, Elisa Isopi, Marilina Codagnone, Veronica Cecilia Mari, Alessia Lamolinara, Marco D'Aurora, Eleonora Cianci, Annalisa Nespoli, Sara Franchi, Valentina Gatta, Marc Dubourdeau, Paolo Moretti, Maria Di Sabatino, Manuela Iezzi, Mario Romano, Antonio Recchiuti. Front. Immunol., 28 April 2020
Differential Profile of Proinflammatory/Proresolving Lipid Mediators in Acute Inflammation Model using Young and Old Skin Biopsies.
Lopez-Gaydon Amandine , Baillif Vincent , Bertholon Cindy , Van Goethem Emeline , Demarne Frédéric , Dubourdeau Marc and Bechetoille Nicolas. Dermatol Res. 2019; 1(1); 1-2
Long chain fatty acids and related pro-inflammatory, specialized pro-resolving lipid mediators and their intermediates in preterm human milk during the first month of lactation.
Robinson DT, Palac HL, Baillif V, Van Goethem E, Dubourdeau M, Van Horn L, Martin CR.- Prostaglandins Leukot Essent Fatty Acids. 2017 Jun - PMID: 28651692
In Vitro and in Vivo Anti-Inflammatory Effect of a Biotechnologically Modified Borage Seed Extract: Evidence for Lipid Pro-Resolving Mediators’ Implication in the Enhancement of Psoriatic and Atopic Dermatitis Lesions
Chene G, Baillif V, Van Goethem E, et al - JCDSA -2015 - DOI: 10.4236/jcdsa.2015.52018
A role for 12/15-lipoxygenase-derived proresolving mediators in postoperative ileus: protectin DX-regulated neutrophil extravasation.
Stein K, Stoffels M, Lysson M, Schneiker B, Dewald O, Krönke G, Kalff JC, Wehner S. - J Leukoc Biol. 2015 Aug 20. PMID: 2629297
Quantification and Potential Functions of Endogenous Agonists of Transient Receptor Potential Channels in Patients With Irritable Bowel Syndrome.
Cenac N,..., Dubourdeau M,et al. - Gastroenterology. 2015 Apr 21. PMID: 25911511
Molecular and cellular profiles of the resolution phase in a damage-associated molecular pattern-mediated peritonitis model and revelation of leukocyte persistence in peritoneal tissues.
Lastrucci C, Baillif V, ..., Dubourdeau M, et al. FASEB J. 2015 Jan 21. PMID: 25609430
Protective effects of n-6 fatty acids-enriched diet on intestinal ischaemia/reperfusion injury involve lipoxin A4 and its receptor.
Gobbetti T, ..., Dubourdeau M, et al. - Br J Pharmacol. 2015 Feb; PMID: 25296998
Polyunsaturated fatty acid metabolism signature in ischemia differs from reperfusion in mouse intestine.
Gobbetti T, ..., Dubourdeau M, et al. - PLoS One. 2013 Sep 20 PMID: 24073272
LC-MS/MS method for rapid and concomitant quantification of pro-inflammatory and pro-resolving polyunsaturated fatty acid metabolites.
Le Faouder P, Baillif V, ..., Chêne G, Guigné C, ..., Dubourdeau M, et al. - J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Aug PMID: 23831705
Relevance of the cyclophosphamide-induced cystitis model for pharmacological studies targeting inflammation and pain of the bladder.
Augé C, Chene G, Dubourdeau M, et al. - Eur J Pharmacol. 2013 May 5 PMID: 23541724
Oral communications
2022
Targeting inflammation and specialized pro-resolving mediators to reinforce barrier function and scalp homeostasis. (co-authorship with Lucas Meyer Cosmetics) (ESDR)
How to resolve Pollution-induced inflammation? (Cosmetotest symposium)
Quantification of inflammation and its resolution by a non-invasive method: dosage of skin bioactive lipids and cytokines (co-authorship with L'Occitane) (Lipids & cosmetics science conference)
2021
From cells to cytokines to health: PNI in translation (co-authorship with Larissa C. Engert, PhD, Harvard Medical School, Sleep and Inflammatory Systems Laboratory) (PNIRS virtual meeting)
2020
Biogenic Synthesis of RvD6 and its Quantification in Skin Biospsies - A Strategy for Analyzing Unavailable but Relevant Biomolecules (Lipids and Cosmetics meeting)
2018
Differential Profiles Of Pro-Inflammatory And Specialized Pro-Resolving Lipid Mediators In PMA-Treated Skin Biopsies From Young And Old Donors (co-authorship with Gattefossé) (IID)
A multicomponent medication promotes inflammation resolution(co-authorship with Biologische Heilmittel Heel GmbH) (NYAS Meeting)
Circadian rythms modulation of senescent skin fibroblasts and impact on the biological functions (co-authorship with Laboratoires Clarins) (SPIM)
2017
Inducing resolution of inflammation to improve skin defense against external aggressions (47th Annual ESDR Meeting)
Resolution of pollution-induced inflammation as an innovative approach for cosmetic actives (COMET)
Monitoring of Pneumocystis jirovecii acquired pneumonia by specialized pro-resolving mediators (World Congress on Inflammation)
Beta Glucans Are Reinforcing the Immune System Through the Mobilization of Resolution Pathways (International Scientific Conference on Probiotics and Prebiotics)
2016
Long chain fatty acids and their related oxylipins in preterm human milk during the first month of lactation (Collaborative work with Daniel T Robinson from Northwestern University Feinberg School of Medicine, Chicago, US) (6th European Workshop on Lipid Mediators)
Glutaminyl cylase (QC) inhibition in a mouse peritonitis model effects eosinophil and macrophage recruitment and levels of resolution molecules (Co-authorship with Torsten Hoffmann & Inge Lues from Probiodrug AG, Germany) (Summer Frontiers Symposium 2016 ‘Systems Biology of Innate Immunity’)
Specialized proresolving mediators and transcriptomic signatures in bleomycin-induced lung fibrosis (ERS International Congress)
Development of a primary human M1 and M2 macrophage model and phagocytosis evaluation of Candida albicans in the presence of lipoxin A4, resolvin D1 and D5 (Miami Symposium on Inflammation 2016 – Best poster prize)
2015
En construction