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Effects of a Novel GPR55 Antagonist on the Arachidonic Acid Cascade in LPS-Activated Primary Microglial Cells

Saliba, Soraya Wilke; Gläser, Franziska 1; Deckers, Anke 2; Keil, Albrecht; Hurrle, Thomas 1; Apweiler, Matthias; Ferver, Florian; Volz, Nicole 1; Endres, Dominique; Bräse, Stefan 1; Fiebich, Bernd L.
1 Institut für Organische Chemie (IOC), Karlsruher Institut für Technologie (KIT)
2 Karlsruher Institut für Technologie (KIT)


Neuroinflammation is a crucial process to maintain homeostasis in the central nervous system (CNS). However, chronic neuroinflammation is detrimental, and it is described in the pathogenesis of CNS disorders, including Alzheimer’s disease (AD) and depression. This process is characterized by the activation of immune cells, mainly microglia. The role of the orphan G-protein-coupled receptor 55 (GPR55) in inflammation has been reported in different models. However, its role in neuroinflammation in respect to the arachidonic acid (AA) cascade in activated microglia is still lacking of comprehension. Therefore, we synthesized a novel GPR55 antagonist (KIT 10, 0.1–25 µM) and tested its effects on the AA cascade in lipopolysaccharide (LPS, 10 ng / mL)-treated primary rat microglia using Western blot and EIAs. We show here that KIT 10 potently prevented the release of prostaglandin $E_{2}$ ($PGE_{2}$), reduced microsomal $PGE_{2}$ synthase (mPGES-1) and cyclooxygenase-2 (COX-2) synthesis, and inhibited the phosphorylation of Ikappa B-alpha (IκB-α), a crucial upstream step of the inflammation-related nuclear factor-kappaB (NF-κB) signaling pathway. ... mehr

Verlagsausgabe §
DOI: 10.5445/IR/1000135342
Veröffentlicht am 14.07.2021
DOI: 10.3390/ijms22052503
Zitationen: 10
Web of Science
Zitationen: 9
Zitationen: 12
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische und Chemische Systeme (IBCS)
Institut für Organische Chemie (IOC)
Publikationstyp Zeitschriftenaufsatz
Publikationsdatum 02.03.2021
Sprache Englisch
Identifikator ISSN: 1422-0067
KITopen-ID: 1000135342
HGF-Programm 43.33.11 (POF IV, LK 01) Adaptive and Bioinstructive Materials Systems
Erschienen in International journal of molecular sciences
Verlag MDPI
Band 22
Heft 5
Seiten Art.-Nr. 2503
Bemerkung zur Veröffentlichung This article belongs to the Special Issue Inflammation in Health and Disease: New Insights and Therapeutic Avenues
Nachgewiesen in Web of Science
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