Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor

Abstract The endogenous fatty acid amide palmitoylethanolamide (PEA) has been shown to exert anti-inflammatory actions mainly through inhibition of the release of pro-inflammatory molecules from mast cells, monocytes and macrophages. Indirect activation of the endocannabinoid (eCB) system is among t...

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Autores principales: F. Guida, L. Luongo, S. Boccella, M. E. Giordano, R. Romano, G. Bellini, I. Manzo, A. Furiano, A. Rizzo, R. Imperatore, F. A. Iannotti, E. D’Aniello, F. Piscitelli, F. sca Rossi, L. Cristino, V. Di Marzo, V. de Novellis, S. Maione
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:8319bd7341c04ac6a900b4788aa3f6e72021-12-02T15:06:07ZPalmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor10.1038/s41598-017-00342-12045-2322https://doaj.org/article/8319bd7341c04ac6a900b4788aa3f6e72017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00342-1https://doaj.org/toc/2045-2322Abstract The endogenous fatty acid amide palmitoylethanolamide (PEA) has been shown to exert anti-inflammatory actions mainly through inhibition of the release of pro-inflammatory molecules from mast cells, monocytes and macrophages. Indirect activation of the endocannabinoid (eCB) system is among the several mechanisms of action that have been proposed to underlie the different effects of PEA in vivo. In this study, we used cultured rat microglia and human macrophages to evaluate whether PEA affects eCB signaling. PEA was found to increase CB2 mRNA and protein expression through peroxisome proliferator-activated receptor-α (PPAR-α) activation. This novel gene regulation mechanism was demonstrated through: (i) pharmacological PPAR-α manipulation, (ii) PPAR-α mRNA silencing, (iii) chromatin immunoprecipitation. Moreover, exposure to PEA induced morphological changes associated with a reactive microglial phenotype, including increased phagocytosis and migratory activity. Our findings suggest indirect regulation of microglial CB2R expression as a new possible mechanism underlying the effects of PEA. PEA can be explored as a useful tool for preventing/treating the symptoms associated with neuroinflammation in CNS disorders.F. GuidaL. LuongoS. BoccellaM. E. GiordanoR. RomanoG. BelliniI. ManzoA. FurianoA. RizzoR. ImperatoreF. A. IannottiE. D’AnielloF. PiscitelliF. sca RossiL. CristinoV. Di MarzoV. de NovellisS. MaioneNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
F. Guida
L. Luongo
S. Boccella
M. E. Giordano
R. Romano
G. Bellini
I. Manzo
A. Furiano
A. Rizzo
R. Imperatore
F. A. Iannotti
E. D’Aniello
F. Piscitelli
F. sca Rossi
L. Cristino
V. Di Marzo
V. de Novellis
S. Maione
Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor
description Abstract The endogenous fatty acid amide palmitoylethanolamide (PEA) has been shown to exert anti-inflammatory actions mainly through inhibition of the release of pro-inflammatory molecules from mast cells, monocytes and macrophages. Indirect activation of the endocannabinoid (eCB) system is among the several mechanisms of action that have been proposed to underlie the different effects of PEA in vivo. In this study, we used cultured rat microglia and human macrophages to evaluate whether PEA affects eCB signaling. PEA was found to increase CB2 mRNA and protein expression through peroxisome proliferator-activated receptor-α (PPAR-α) activation. This novel gene regulation mechanism was demonstrated through: (i) pharmacological PPAR-α manipulation, (ii) PPAR-α mRNA silencing, (iii) chromatin immunoprecipitation. Moreover, exposure to PEA induced morphological changes associated with a reactive microglial phenotype, including increased phagocytosis and migratory activity. Our findings suggest indirect regulation of microglial CB2R expression as a new possible mechanism underlying the effects of PEA. PEA can be explored as a useful tool for preventing/treating the symptoms associated with neuroinflammation in CNS disorders.
format article
author F. Guida
L. Luongo
S. Boccella
M. E. Giordano
R. Romano
G. Bellini
I. Manzo
A. Furiano
A. Rizzo
R. Imperatore
F. A. Iannotti
E. D’Aniello
F. Piscitelli
F. sca Rossi
L. Cristino
V. Di Marzo
V. de Novellis
S. Maione
author_facet F. Guida
L. Luongo
S. Boccella
M. E. Giordano
R. Romano
G. Bellini
I. Manzo
A. Furiano
A. Rizzo
R. Imperatore
F. A. Iannotti
E. D’Aniello
F. Piscitelli
F. sca Rossi
L. Cristino
V. Di Marzo
V. de Novellis
S. Maione
author_sort F. Guida
title Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor
title_short Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor
title_full Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor
title_fullStr Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor
title_full_unstemmed Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor
title_sort palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the cb2 receptor
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/8319bd7341c04ac6a900b4788aa3f6e7
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