Expression of Cannabinoid Receptor GPR55 in Human Gingival Fibroblasts and Anti-inflammatory Effects of Cannabidiol via GPR55

Abstract

: Cannabidiol (CBD) in cannabis has an anti-inflammatory effect, and its receptor, G protein-coupled receptor 55 (GPR55), has been suggested to be involved in the regulation of inflammation. Here, we investigated GPR55 expression in human gingival fibroblasts (HGFs) and anti-inflammatory effects of CBD via GPR55. GPR55 expression and localization were confirmed in control, LPS-stimulated (LPS), CBD-treated and LPS-stimulated (CBD ＋ LPS), and CBD-treated (CBD) groups. We also compared interleukin (IL)-6 and IL-8 protein production in each group. GPR55 expression levels were significantly reduced in the LPS and CBD ＋ LPS groups (p ＜ 0.05) compared to control and CBD groups, and GPR55 protein was found diffusely in the cytoplasm of HGFs in all groups. In addition, IL-6 and IL-8 production was significantly reduced in non-knockdown HGFs in the CBD ＋ LPS group compared to the LPS group (p ＜ 0.05). By contrast, in GPR55-knockdown HGFs, there was a significant increase in IL-6 and IL-8 production in the LPS and CBD ＋ LPS groups compared with the control groups (p ＜ 0.05), but there was no significant difference in IL-6 and IL-8 production in GPR 55-knockdown HGFs between the LPS and CBD ＋ LPS groups. In this study, we confirmed the homeostatic expression of GPR55 in HGFs and its tendency to decrease in expression during inflammation. It was also shown that part of an anti-inflammatory effect by CBD may be mediated by GPR55.