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Sci Rep. 2017 Mar 23;7(1):375. doi: 10.1038/s41598-017-00342-1.

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

Author information

1
Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Università degli Studi della Campania "Luigi Vanvitelli" (Ex SUN), 80138, Naples, Italy.
2
Endocannabinoid Research Group, Institute of Biomolecular Chemistry, C.N.R., Pozzuoli, Italy.
3
Department of Women, Child and General and Specialistic Surgery, Università degli Studi della Campania "Luigi Vanvitelli" (Ex SUN), 80138, Naples, Italy.
4
Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Università degli Studi della Campania "Luigi Vanvitelli" (Ex SUN), 80138, Naples, Italy.
5
Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy.
6
Department of Science and Technology, University of Sannio, Benevento, Italy.
7
Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Università degli Studi della Campania "Luigi Vanvitelli" (Ex SUN), 80138, Naples, Italy. sabatino.maione@unina2.it.
8
Endocannabinoid Research Group, Institute of Biomolecular Chemistry, C.N.R., Pozzuoli, Italy. sabatino.maione@unina2.it.

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.

PMID:
28336953
PMCID:
PMC5428303
DOI:
10.1038/s41598-017-00342-1
[Indexed for MEDLINE]
Free PMC Article

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