Anti-Inflammatory Effects of GPR55 Agonists and Antagonists in LPS-Treated BV2 Microglial Cells

Chronic inflammation is driven by proinflammatory cytokines such as interleukin 6 (IL-6),
tumor necrosis factor-α (TNF-α), and chemokines, such as c-c motif chemokine ligand 2 (CCL2),
CCL3, C-X-C motif chemokine ligand 2 (CXCL2), and CXCL10. Inflammatory processes of the
central nervous system (CNS) play an important role in the pathogenesis of various neurological
and psychiatric disorders like Alzheimer’s disease, Parkinson’s disease, and depression. Therefore,
identifying novel anti-inflammatory drugs may be beneficial for treating disorders with a neuroin-
flammatory background. The G-protein-coupled receptor 55 (GPR55) gained interest due to its role in
inflammatory processes and possible involvement in different disorders. This study aims to identify
the anti-inflammatory effects of the coumarin-based compound KIT C, acting as an antagonist with
inverse agonistic activity at GPR55, in lipopolysaccharide (LPS)-stimulated BV2 microglial cells
in comparison to the commercial GPR55 agonist O-1602 and antagonist ML-193. All compounds
significantly suppressed IL-6, TNF-α, CCL2, CCL3, CXCL2, and CXCL10 expression and release
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in LPS-treated BV2 microglial cells. The anti-inflammatory effects of the compounds are partially
explained by modulation of the phosphorylation of p38 mitogen-activated protein kinase (MAPK),
p42/44 MAPK (ERK 1/2), protein kinase C (PKC) pathways, and the transcription factor nuclear
factor (NF)-κB, respectively. Due to its potent anti-inflammatory properties, KIT C is a promising
compound for further research and potential use in inflammatory-related disorders.