Back to Search Start Over

Anti-neuroinflammatory effects of GPR55 antagonists in LPS-activated primary microglial cells.

Authors :
Saliba, Soraya Wilke
Jauch, Hannah
Gargouri, Brahim
Keil, Albrecht
Hurrle, Thomas
Volz, Nicole
Mohr, Florian
van der Stelt, Mario
Bräse, Stefan
Fiebich, Bernd L.
Source :
Journal of Neuroinflammation; 11/19/2018, Vol. 15 Issue 1, pN.PAG-N.PAG, 1p
Publication Year :
2018

Abstract

<bold>Background: </bold>Neuroinflammation plays a vital role in Alzheimer's disease and other neurodegenerative conditions. Microglia are the resident mononuclear immune cells of the central nervous system, and they play essential roles in the maintenance of homeostasis and responses to neuroinflammation. The orphan G-protein-coupled receptor 55 (GPR55) has been reported to modulate inflammation and is expressed in immune cells such as monocytes and microglia. However, its effects on neuroinflammation, mainly on the production of members of the arachidonic acid pathway in activated microglia, have not been elucidated in detail.<bold>Methods: </bold>In this present study, a series of coumarin derivatives, that exhibit GPR55 antagonism properties, were designed. The effects of these compounds on members of the arachidonic acid cascade were studied in lipopolysaccharide (LPS)-treated primary rat microglia using Western blot, qPCR, and ELISA.<bold>Results: </bold>We demonstrate here that the various compounds with GPR55 antagonistic activities significantly inhibited the release of PGE2 in primary microglia. The inhibition of LPS-induced PGE2 release by the most potent candidate KIT 17 was partially dependent on reduced protein synthesis of mPGES-1 and COX-2. KIT 17 did not affect any key enzyme involved on the endocannabinoid system. We furthermore show that microglia expressed GPR55 and that a synthetic antagonist of the GPR receptor (ML193) demonstrated the same effect of the KIT 17 on the inhibition of PGE2.<bold>Conclusions: </bold>Our results suggest that KIT 17 is acting as an inverse agonist on GPR55 independent of the endocannabinoid system. Targeting GPR55 might be a new therapeutic option to treat neurodegenerative diseases with a neuroinflammatory background such as Alzheimer's disease, Parkinson, and multiple sclerosis (MS). [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
17422094
Volume :
15
Issue :
1
Database :
Complementary Index
Journal :
Journal of Neuroinflammation
Publication Type :
Academic Journal
Accession number :
133089588
Full Text :
https://doi.org/10.1186/s12974-018-1362-7