The CB2-PKC pathway is involved in esketamine-induced anti-inflammation in BV-2 microglial cells exposed to lipopolysaccharides.
Yuqing Wang, Ming Cao, Yuanyuan Zhang, Qian Chen, Zhaojie Chen, Ji Jia
American journal of translational research January 1, 2024 DOI: 10.62347/RRZF5229 via PubMed
Summary
Esketamine reduces inflammation in microglial cells stimulated with lipopolysaccharide, a bacterial toxin that mimics neuroinflammation. The anti-inflammatory effect involves upregulation of the cannabinoid type 2 (CB2) receptor and activation of protein kinase C (PKC). Blocking either the CB2 receptor with AM630 or PKC with chelerythrine reversed esketamine's ability to lower proinflammatory cytokines, nitrite, iNOS, and NF-κB (p65) expression. These results suggest the microglial CB2-PKC pathway mediates esketamine's anti-inflammatory actions, offering a potential mechanism for its antidepressant effects beyond direct neurotransmitter modulation.
Study at a glance
| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | BV-2 microglial cells |
| Intervention | Esketamine |
| Topics | Depression Ketamine |
| Keywords | Cannabinoid cb2 receptor Lipopolysaccharide Microglia Neuroinflammation |
| Citations | 3 |
| Key finding | Esketamine reduces lipopolysaccharide-induced neuroinflammation in microglial cells through the CB2 receptor and protein kinase C pathway. |
Abstract
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. 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. 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. These observations demonstrated that the microglial CB2-PKC pathway mediates ESK-induced anti-inflammation in LPS-stimulated microglial cells.