The CB2-PKC pathway is involved in esketamine-induced anti-inflammation in BV-2 microglial cells exposed to lipopolysaccharides.

Abstract

<h4>Objective</h4>Esketamine (ESK), an intravenous anesthetic, exerts antidepressant effects; however, the antidepression mechanism is not clear. The aim of this study was to explore whether microglial cannabinoid type 2 (CB2) receptor and protein kinase C (PKC) are involved in the antidepressant effects of ESK.<h4>Methods</h4>In this investigation, lipopolysaccharide (LPS) was used to stimulate BV-2 microglia to mimic neuroinflammation. An enzyme-linked immunosorbent assay (ELISA) and Griess reagent kits were used to determine cytokine and nitrite concentrations in the medium. CB2, inducible nitric oxide synthase (iNOS) and nuclear factor (NF)-κB (p65) protein expression were evaluated by immunocytochemistry and western blot analysis.<h4>Results</h4>Compared with the control, LPS enhanced proinflammatory factor and nitrite concentration in the medium, upregulated iNOS and NF-κB (p65) expressions, and coadministration of ESK decreased proinflammatory cytokine and nitrite levels, and downregulated iNOS and NF-κB (p65) expression. Moreover, ESK exposure enhanced CB2 receptor expression; coadministration of the CB2 receptor antagonist AM630 or the PKC inhibitor chelerythrine (Che), however, markedly blocked the anti-inflammatory effect of ESK in reducing cytokine and nitrite concentration, and downregulating iNOS and NF-κB (p65) expression.<h4>Conclusions</h4>These observations demonstrated that the microglial CB2-PKC pathway mediates ESK-induced anti-inflammation in LPS-stimulated microglial cells.

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