银屑病是一种慢性炎症性皮肤疾病。炎症和氧化应激在银屑病的发病机制中起着至关重要的作用。大麻素受体类型2（CB2R）是治疗各种炎症性疾病的有吸引力的靶点。然而，CB2R激活在银屑病中的确切作用和机制仍需进一步阐明。本研究使用 Imiquimod（IMQ）诱导的实验性银屑病小鼠和肿瘤坏死因子-α（TNF-α）激活的角质细胞（HaCaT）来检查CB2R激活对体内和体外银屑病样损伤的影响及其机制。我们的结果表明，使用特定激动剂GW842166X（GW）激活CB2R在显著减少小鼠IMQ诱导的银屑病样皮肤损伤方面发挥了重要作用，通过减少表皮厚度和减少斑块厚度。一方面，GW通过减少炎症细胞浸润和炎性细胞因子减轻炎症反应。另一方面，该治疗减少了iNOS水平并下调了银屑病皮肤组织中CB2R的表达。进一步的研究表明，拟茎芽样ECH相关蛋白1/ nrf2（Keap1/Nrf2）信号通路可能参与其中。我们的研究发现，CB2R的选择性激活可能作为银屑病治疗的一种新策略。 © 2023年。作者(们)已授予Springer Science+Business Media,LLC,Springer Nature的独家许可。

Psoriasis is a chronic inflammatory skin disease. Inflammation and oxidative stress play crucial roles in the pathogenesis of psoriasis. Cannabinoid receptor type 2 (CB2R) is an attractive target for treating various inflammatory disorders. However, the precise role and mechanism of CB2R activation in psoriasis remain to be further elucidated. In this study, imiquimod (IMQ)-induced experimental psoriasis mice and tumor necrosis factor-α (TNF-α)-activated keratinocytes (HaCaT) were used to examine the effect of CB2R activation on psoriasis-like lesions and the mechanism in vivo and in vitro. Our results demonstrated that activation of CB2R by the specific agonist GW842166X (GW) significantly ameliorated IMQ-induced psoriasiform skin lesions in mice by reducing epidermal thickness and decreasing plaque thickness. On the one hand, GW alleviated inflammation by decreasing inflammatory cytokines and abating inflammatory cell infiltration. On the other hand, this treatment reduced the level of iNOS and downregulated the expression of CB2R in psoriatic skin tissue. Further studies suggested that the Kelch-like ECH-associated protein 1/nuclear factor erythroid-2-related factor (Keap1/Nrf2) signaling pathway might be involved. Our findings reveal that selective activation of CB2R may serve as a new strategy for the treatment of psoriasis.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.