Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Pozzuoli, Napoli, Italy (S.P., R.V., M.A., V.D.); Epitech Group SpA, Saccolongo, Padova, Italy (S.P., M.A.); and Dipartimento di Farmacologia Sperimentale, Università di Napoli "Federico II", Napoli, Italy (M.V., T.I.).
Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Pozzuoli, Napoli, Italy (S.P., R.V., M.A., V.D.); Epitech Group SpA, Saccolongo, Padova, Italy (S.P., M.A.); and Dipartimento di Farmacologia Sperimentale, Università di Napoli "Federico II", Napoli, Italy (M.V., T.I.)
J Pharmacol Exp Ther. 2018 Jun;365(3):652-663. doi: 10.1124/jpet.117.244368. Epub 2018 Apr 9.
Phytocannabinoids modulate inflammatory responses by regulating the production of cytokines in several experimental models of inflammation. Cannabinoid type-2 (CB) receptor activation was shown to reduce the production of the monocyte chemotactic protein-2 (MCP-2) chemokine in polyinosinic-polycytidylic acid [poly-(I:C)]-stimulated human keratinocyte (HaCaT) cells, an in vitro model of allergic contact dermatitis (ACD). We investigated if nonpsychotropic cannabinoids, such as cannabidiol (CBD), produced similar effects in this experimental model of ACD. HaCaT cells were stimulated with poly-(I:C), and the release of chemokines and cytokines was measured in the presence of CBD or other phytocannabinoids (such as cannabidiol acid, cannabidivarin, cannabidivarinic acid, cannabichromene, cannabigerol, cannabigerolic acid, cannabigevarin, tetrahydrocannabivarin, and tetrahydrocannabivarinic acid) and antagonists of CB, CB, or transient receptor potential vanilloid type-1 (TRPV1) receptors. HaCaT cell viability following phytocannabinoid treatment was also measured. The cellular levels of endocannabinoids [anandamide (AEA), 2-arachidonoylglycerol] and related molecules (palmitoylethanolamide, oleoylethanolamide) were quantified in poly-(I:C)-stimulated HaCaT cells treated with CBD. We show that in poly-(I:C)-stimulated HaCaT cells, CBD elevates the levels of AEA and dose-dependently inhibits poly-(I:C)-induced release of MCP-2, interleukin-6 (IL-6), IL-8, and tumor necrosis factor- in a manner reversed by CB and TRPV1 antagonists 6-iodopravadoline (AM630) and 5'-iodio-resiniferatoxin (I-RTX), respectively, with no cytotoxic effect. This is the first demonstration of the anti-inflammatory properties of CBD in an experimental model of ACD.
植物大麻素通过调节几种炎症模型中细胞因子的产生来调节炎症反应。已经表明，大麻素 2 型 (CB) 受体的激活可减少多聚肌苷酸-多聚胞苷酸 [多聚-(I:C)] 刺激的人角质形成细胞 (HaCaT) 细胞中单核细胞趋化蛋白-2 (MCP-2) 趋化因子的产生，这是一种过敏性接触性皮炎 (ACD) 的体外模型。我们研究了非精神活性大麻素，如大麻二酚 (CBD)，在这种 ACD 的实验模型中是否会产生类似的作用。用多聚-(I:C)刺激 HaCaT 细胞，并在 CBD 或其他植物大麻素（如大麻二酚酸、大麻二酚、大麻二酚酸、大麻色烯、大麻二醇、大麻二醇酸、大麻比咯嗪、四氢大麻酚、四氢大麻酚酸）存在的情况下测量趋化因子和细胞因子的释放和 CB、CB 或瞬时受体电位香草醛型-1 (TRPV1) 受体的拮抗剂。还测量了植物大麻素处理后 HaCaT 细胞活力。用 CBD 处理多聚-(I:C)刺激的 HaCaT 细胞后，量化了细胞内大麻素 [花生四烯酸酰胺 (AEA)、2-花生四烯酰甘油] 和相关分子 (棕榈酰乙醇酰胺、油酰乙醇酰胺) 的水平。我们表明，在多聚-(I:C)刺激的 HaCaT 细胞中，CBD 升高 AEA 的水平，并以剂量依赖性方式抑制多聚-(I:C)诱导的 MCP-2、白细胞介素-6 (IL-6)、IL-8 和肿瘤坏死因子-α的释放，这种方式可被 CB 和 TRPV1 拮抗剂 6-碘普拉地洛 (AM630) 和 5'-碘树脂毒素 (I-RTX) 逆转，分别为，没有细胞毒性作用。这是 CBD 在 ACD 实验模型中抗炎特性的首次证明。
