239 The role of phytocannabinoids on monocyte-derived dendritic cells differentiation and maturation

Abstract

Dendritic cells (DCs) act as a major link between the innate and adaptive immune systems. Nowadays, as the use of herbal active ingredients from the cannabis plant (Cannabis sativa) is gaining in popularity, the use of these products has shown an exponential increase, even in topical formulations that can directly influence the main function of DCs in skin. Up to now more than 100 different cannabinoids have been isolated from the Cannabis plant, which are called phytocannabinoids (PCs). PCs, especially the non-psychoactive compounds, have been shown to have beneficial effects in multiple inflammatory disease models; nevertheless, they were mostly investigated in mouse models and not on human cells. In our current work, we investigated the effect of four non-psychoactive PCs (cannabidiol, cannabinol, cannabigerol, tetrahydrocannabivarin, in regulating responses of monocyte-derived DCs by monitoring changes in their maturation markers. First, to exclude the possibility of the onset of early apoptotic or necrotic processes, we performed viability tests (PrestoBlue and G6PDH release assay), which demonstrated that our PCs did not cause any cell death of moDC. Moreover, we found that our PCs generally induced cell maturation at high concentrations on moDC, whereas LPS-induced maturation was not affected. Furthermore, we also found that CBG and THCV lead to an increase in the endocytotic capability of iDCs. Interestingly the increased maturation of the cells upon PC treatment did not result in inflammatory mediator production, however LPC-induced mediator production was enhanced by PCs. PCs also increased DC-induced T cell proliferation. Taken together, our data suggest that PCs may play varied roles on the immunological function of moDCs, and their use as potent anti-inflammatory treatments must be tested extensively.