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

Saliba, S. W.; Jauch, H.; Gargouri, B.; Keil, A.; Hurrle, T.; Volz, N.; Mohr, F.; Stelt, M. van der; Bräse, S.; Fiebich, B. L.

Background: 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.
Methods: 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.
Results: 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. ... mehr

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Verlagsausgabe §
DOI: 10.5445/IR/1000088203
Veröffentlicht am 05.12.2018
DOI: 10.1186/s12974-018-1362-7
Zitationen: 19
Web of Science
Zitationen: 19
Zitationen: 17
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Organische Chemie (IOC)
Institut für Toxikologie und Genetik (ITG)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2018
Sprache Englisch
Identifikator ISSN: 1742-2094
KITopen-ID: 1000088203
HGF-Programm 47.01.01 (POF III, LK 01) Biol.Netzwerke u.Synth.Regulat. ITG+ITC
Erschienen in Journal of neuroinflammation
Verlag BioMed Central (BMC)
Band 15
Heft 1
Seiten Art. Nr.: 322
Schlagwörter GPR55, Prostaglandin E2, Cyclooxygenase, Microglia, Neuroinflammation
Nachgewiesen in Dimensions
Web of Science
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