Cannabinoid receptor modulation of the endothelial cell inflammatory response (P4191)

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Abstract The cannabinoid receptor (CBR) family is composed of the G-protein coupled receptors, CB1R and CB2R, and potentially GPR18, GPR55 and GPR119, and the transient receptor potential ion channel, TRPV1. Recent reports suggest that several cannabinoids have the ability to modulate the activation of the endothelium in response to inflammatory mediators; however, it is not clear which receptors and what mechanisms are responsible. Our studies aim to determine: 1) the expression repertoire of CBRs in different human endothelial cell (EC) niches; and 2) determine which cannabinoid receptors are responsible for modulating EC activation by toll-like receptor agonists and TNFα. Through qPCR analysis, we have found that all ECs express the same subset of CBRs. Additionally, by utilizing a panel of synthetic, endogenous and plant-derived cannabinoids with differing specificities for each CBR, our data thus far suggest that CB1R and/or TRPV1 activation may be responsible for dampening the inflammatory activation of ECs by TLR2 agonists, as determined by a decrease in IL-6 and IL-8 secretion. Future studies aim to definitively identify the CBR(s) responsible, determine the effect of phytocannabinoids on EC activation in more detail, delineate the cellular mechanisms by which CBRs modulate the EC inflammatory response and more globally, identify the role of endocannabinoids and their receptors in modulation of the inflammatory response to infection.