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Specific Activation of CB2R Ameliorates Psoriasis-Like Skin Lesions by Inhibiting Inflammation and Oxidative Stress

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Abstract

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.

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Acknowledgements

The authors acknowledge Xia Lei, director of the Department of Dermatovenerology of Daping Hospital, for her warm help to our work. The authors also acknowledge Haigang Zhang, director of the Department of Pharmacology of Army Medical University, for supporting this study.

Funding

This work was supported by the National Natural Science Foundation of China (Grant number: 82174061).

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Authors and Affiliations

  1. Department of Dermatology, Daping Hospital, Army Medical University, Chongqing, 400042, China

    He Yufeng, Jia Honglin, Huang Xianqiong & Sun Renshan

  2. Department of Pharmacology, College of Pharmacy and Laboratory Medicine, Army Medical University, Chongqing, 400038, China

    Yang Qunfang, Shan Wenjun, Chen Xiaohong & Liu Tao

  3. Department of Dermatology, Health Science Center, South China Hospital, Shenzhen University, Guangdong, 518116, China

    Sun Renshan

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Contributions

Tao Liu and Renshan Sun designed the experiments. Yufeng He and Honglin Jia performed experiments. Xiaohong Chen and Wenjun Shan contributed to preparing reagents, materials, and experimental equipment. Tao Liu, Yufeng He, Qunfang Yang and Xianqiong Huang analyzed the data. Yufeng He and Tao Liu wrote the article. Tao Liu and Renshan Sun revised the article. All authors read and approved the final article.

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Correspondence to Liu Tao or Sun Renshan.

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He, Y., Jia, H., Yang, Q. et al. Specific Activation of CB2R Ameliorates Psoriasis-Like Skin Lesions by Inhibiting Inflammation and Oxidative Stress. Inflammation 46, 1255–1271 (2023). https://doi.org/10.1007/s10753-023-01805-6

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