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Specialized pro-resolving lipid mediators are differentially altered in peripheral blood of patients with multiple sclerosis and attenuate monocyte and blood-brain barrier dysfunction

Chronic inflammation is a key pathological hallmark of multiple sclerosis (MS) and suggests that resolution of inflammation, orchestrated by specialized pro-resolving lipid mediators (LM), is impaired. Here, through targeted-metabololipidomics in peripheral blood of patients with MS, we revealed tha...

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Autores principales: Kooij, Gijs, Troletti, Claudio Derada, Leuti, Alessandro, Norris, Paul C., Riley, Ian, Albanese, Maria, Ruggieri, Serena, Libreros, Stephania, van der Pol, Susanne M.A., van het Hof, Bert, Schell, Yoelle, Guerrera, Gisella, Buttari, Fabio, Mercuri, Nicola Biagio, Centonze, Diego, Gasperini, Claudio, Battistini, Luca, de Vries, Helga E., Serhan, Charles N., Chiurchiù, Valerio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395264/
https://www.ncbi.nlm.nih.gov/pubmed/31780628
http://dx.doi.org/10.3324/haematol.2019.219519
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author Kooij, Gijs
Troletti, Claudio Derada
Leuti, Alessandro
Norris, Paul C.
Riley, Ian
Albanese, Maria
Ruggieri, Serena
Libreros, Stephania
van der Pol, Susanne M.A.
van het Hof, Bert
Schell, Yoelle
Guerrera, Gisella
Buttari, Fabio
Mercuri, Nicola Biagio
Centonze, Diego
Gasperini, Claudio
Battistini, Luca
de Vries, Helga E.
Serhan, Charles N.
Chiurchiù, Valerio
author_facet Kooij, Gijs
Troletti, Claudio Derada
Leuti, Alessandro
Norris, Paul C.
Riley, Ian
Albanese, Maria
Ruggieri, Serena
Libreros, Stephania
van der Pol, Susanne M.A.
van het Hof, Bert
Schell, Yoelle
Guerrera, Gisella
Buttari, Fabio
Mercuri, Nicola Biagio
Centonze, Diego
Gasperini, Claudio
Battistini, Luca
de Vries, Helga E.
Serhan, Charles N.
Chiurchiù, Valerio
author_sort Kooij, Gijs
collection PubMed
description Chronic inflammation is a key pathological hallmark of multiple sclerosis (MS) and suggests that resolution of inflammation, orchestrated by specialized pro-resolving lipid mediators (LM), is impaired. Here, through targeted-metabololipidomics in peripheral blood of patients with MS, we revealed that each disease form was associated with distinct LM profiles that significantly correlated with disease severity. In particular, relapsing and progressive MS patients were associated with high eicosanoids levels, whereas the majority of pro-resolving LM were significantly reduced or below limits of detection and correlated with disease progression. Furthermore, we found impaired expression of several pro-resolving LM biosynthetic enzymes and receptors in blood-derived leukocytes of MS patients. Mechanistically, differentially expressed mediators like LXA4, LXB4, RvD1 and PD1 reduced MS-derived monocyte activation and cytokine production, and inhibited inflammation-induced blood-brain barrier dysfunction and monocyte transendothelial migration. Altogether, these findings reveal peripheral defects in the resolution pathway in MS, suggesting pro-resolving LM as novel diagnostic biomarkers and potentially safe therapeutics.
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spelling pubmed-73952642020-08-07 Specialized pro-resolving lipid mediators are differentially altered in peripheral blood of patients with multiple sclerosis and attenuate monocyte and blood-brain barrier dysfunction Kooij, Gijs Troletti, Claudio Derada Leuti, Alessandro Norris, Paul C. Riley, Ian Albanese, Maria Ruggieri, Serena Libreros, Stephania van der Pol, Susanne M.A. van het Hof, Bert Schell, Yoelle Guerrera, Gisella Buttari, Fabio Mercuri, Nicola Biagio Centonze, Diego Gasperini, Claudio Battistini, Luca de Vries, Helga E. Serhan, Charles N. Chiurchiù, Valerio Haematologica Article Chronic inflammation is a key pathological hallmark of multiple sclerosis (MS) and suggests that resolution of inflammation, orchestrated by specialized pro-resolving lipid mediators (LM), is impaired. Here, through targeted-metabololipidomics in peripheral blood of patients with MS, we revealed that each disease form was associated with distinct LM profiles that significantly correlated with disease severity. In particular, relapsing and progressive MS patients were associated with high eicosanoids levels, whereas the majority of pro-resolving LM were significantly reduced or below limits of detection and correlated with disease progression. Furthermore, we found impaired expression of several pro-resolving LM biosynthetic enzymes and receptors in blood-derived leukocytes of MS patients. Mechanistically, differentially expressed mediators like LXA4, LXB4, RvD1 and PD1 reduced MS-derived monocyte activation and cytokine production, and inhibited inflammation-induced blood-brain barrier dysfunction and monocyte transendothelial migration. Altogether, these findings reveal peripheral defects in the resolution pathway in MS, suggesting pro-resolving LM as novel diagnostic biomarkers and potentially safe therapeutics. Fondazione Ferrata Storti 2020-08 /pmc/articles/PMC7395264/ /pubmed/31780628 http://dx.doi.org/10.3324/haematol.2019.219519 Text en Copyright© 2020 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article
Kooij, Gijs
Troletti, Claudio Derada
Leuti, Alessandro
Norris, Paul C.
Riley, Ian
Albanese, Maria
Ruggieri, Serena
Libreros, Stephania
van der Pol, Susanne M.A.
van het Hof, Bert
Schell, Yoelle
Guerrera, Gisella
Buttari, Fabio
Mercuri, Nicola Biagio
Centonze, Diego
Gasperini, Claudio
Battistini, Luca
de Vries, Helga E.
Serhan, Charles N.
Chiurchiù, Valerio
Specialized pro-resolving lipid mediators are differentially altered in peripheral blood of patients with multiple sclerosis and attenuate monocyte and blood-brain barrier dysfunction
title Specialized pro-resolving lipid mediators are differentially altered in peripheral blood of patients with multiple sclerosis and attenuate monocyte and blood-brain barrier dysfunction
title_full Specialized pro-resolving lipid mediators are differentially altered in peripheral blood of patients with multiple sclerosis and attenuate monocyte and blood-brain barrier dysfunction
title_fullStr Specialized pro-resolving lipid mediators are differentially altered in peripheral blood of patients with multiple sclerosis and attenuate monocyte and blood-brain barrier dysfunction
title_full_unstemmed Specialized pro-resolving lipid mediators are differentially altered in peripheral blood of patients with multiple sclerosis and attenuate monocyte and blood-brain barrier dysfunction
title_short Specialized pro-resolving lipid mediators are differentially altered in peripheral blood of patients with multiple sclerosis and attenuate monocyte and blood-brain barrier dysfunction
title_sort specialized pro-resolving lipid mediators are differentially altered in peripheral blood of patients with multiple sclerosis and attenuate monocyte and blood-brain barrier dysfunction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395264/
https://www.ncbi.nlm.nih.gov/pubmed/31780628
http://dx.doi.org/10.3324/haematol.2019.219519
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