Anti-inflammatory Activity of Cannabinoid Receptor 2 Ligands in Primary hPDL Fibroblasts

Publication date: Available online 6 December 2017
Source:Archives of Oral Biology
Author(s): Ammaar H. Abidi, Chaela S. Presley, Mustafa Dabbous, David A. Tipton, Suni M. Mustafa, Bob M. Moore II
ObjectivesApproximately 65 million adults in the US have periodontitis, causing tooth loss and decreased quality of life. Cannabinoids modulate immune responses, and endocannabinoids are prevalent during oral cavity inflammation. Targets for intervention in periodontal inflammation are cannabinoid type 1 and 2 receptors (CB1R, CB2R), particularly CB2R because its levels increase during inflammation. We previously demonstrated that SMM-189 (CB2R inverse agonist) decreased pro-inflammatory cytokine production in primary microglial cells. The hypothesis of this study was that cannabinoids anandamide (AEA), HU308 (CB2R selective agonist), and SMM-189 decrease pro-inflammatory IL-6 and MCP-1 production by primary human periodontal ligament fibroblasts (hPDLFs) stimulated with P.gingivalis LPS, TNFα, or IL-1β.DesignCytotoxic effects of cannabinoid compounds (10⁻⁴ −10^−6.5M), LPS (1–1000ng/ml), TNFα (10ng/ml) and IL-1β (1ng/ml) were assessed by measuring effects on cellular dehydrogenase activity. IL-6 and MCP-1 production were measured using Mesoscale Discovery (MSD) Human Pro-Inflammatory IL-6 and MSD Human Chemokine MCP-1 kits and analyzed using MSD Sector 2400 machine.ResultsEC50 values for AEA, SMM-189, and HU308 were 16μM, 13μM, and 7.3μM respectively. LPS (1μg/ml), TNFα (10ng/ml), and IL-1β (1ng/ml) increased IL-6 and MCP-1 production, which were inhibited by AEA, SMM-189, and HU308. AEA alone significantly increased IL-6, but not MCP-1 levels, but the other cannabinoids alone had no effect.ConclusionThe effective inhibition of LPS, TNFα, IL-1β-stimulated IL-6 and MCP-1 production by CB2R ligands in hPDLFs suggests that targeting the endocannabinoid system may lead to development of novel drugs for periodontal therapy, aiding strategies to improve oral health.



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