Laboratory of Experimental Dermatology, Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
Allergy. 2013 Aug;68(8):994-1000. doi: 10.1111/all.12183. Epub 2013 Jul 29.
∆(9) -Tetrahydrocannabinol (THC), the active constituent of Cannabis sativa, exerts its biological effects in part through the G-protein-coupled CB1 and CB2 receptors, which were initially discovered in brain and spleen tissue, respectively. However, THC also has CB1/2 receptor-independent effects. Because of its immune-inhibitory potential, THC and related cannabinoids are being considered for the treatment of inflammatory skin diseases. Here we investigated the mechanism of the anti-inflammatory activity of THC and the role of CB1 and CB2 receptors.
We evaluated the impact of topically applied THC on DNFB-mediated allergic contact dermatitis in wild-type and CB1/2 receptor-deficient mice. We performed immunohistochemical analyses for infiltrating immune cells and studied the influence of THC on the interaction between T cells, keratinocytes and myeloid immune cells in vitro.
Topical THC application effectively decreased contact allergic ear swelling and myeloid immune cell infiltration not only in wild-type but also in CB1/2 receptor-deficient mice. We found that THC (1) inhibited the production of IFNγ by T cells, (2) decreased the production of CCL2 and of IFNγ-induced CCL8 and CXL10 by epidermal keratinocytes and (3) thereby limited the recruitment of myeloid immune cells in vitro in a CB1/2 receptor-independent manner.
Topically applied THC can effectively attenuate contact allergic inflammation by decreasing keratinocyte-derived pro-inflammatory mediators that orchestrate myeloid immune cell infiltration independent of CB1/2 receptors. This has important implications for the future development of strategies to harness cannabinoids for the treatment of inflammatory skin diseases.
Δ(9)-四氢大麻酚（THC）是大麻的活性成分，它通过 G 蛋白偶联的 CB1 和 CB2 受体发挥部分生物效应，这两种受体最初分别在大脑和脾脏组织中发现。然而，THC 也具有 CB1/2 受体非依赖性作用。由于其免疫抑制潜力，THC 和相关大麻素正被考虑用于治疗炎症性皮肤病。在这里，我们研究了 THC 的抗炎活性的机制以及 CB1 和 CB2 受体的作用。
我们评估了局部应用 THC 对 DNFB 介导的过敏性接触性皮炎在野生型和 CB1/2 受体缺陷型小鼠中的影响。我们进行了免疫组织化学分析，以评估浸润性免疫细胞，并研究了 THC 对 T 细胞、角质形成细胞和髓样免疫细胞之间相互作用的影响。
局部应用 THC 不仅能有效减轻野生型小鼠，而且能减轻 CB1/2 受体缺陷型小鼠的接触性过敏耳肿胀和髓样免疫细胞浸润。我们发现 THC（1）抑制 T 细胞产生 IFNγ，（2）减少角质形成细胞产生 CCL2 和 IFNγ诱导的 CCL8 和 CXL10，（3）从而以 CB1/2 受体非依赖性方式限制髓样免疫细胞在体外的募集。
局部应用 THC 可通过减少角质形成细胞衍生的促炎介质来有效减轻接触性过敏炎症，这些介质可协调髓样免疫细胞浸润，而不依赖于 CB1/2 受体。这对未来利用大麻素治疗炎症性皮肤病的策略的发展具有重要意义。
