Lin Lixian, Huang Zhongzhou, Jianchi Ma, Guo Zhixuan, Shi Zhenrui, Tang Zengqi, Guo Qing, Xiong Hui
Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Dermatology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
Clin Exp Pharmacol Physiol. 2023 Nov;50(11):903-913. doi: 10.1111/1440-1681.13816. Epub 2023 Aug 27.
Artesunate (ART), an antimalarial drug with a multifunctional immunomodulatory effect, reduces psoriasis disease. ART can alleviate psoriasis-like dermatitis in mice but has no effect on proinflammatory cytokines in the blood. Thus, we hypothesized that the skin might be the target tissue of ART during the treatment of psoriasis. The interleukin (IL)-23/IL-17 axis has a key role in the pathogenesis of psoriasis. However, whether and how ART manipulates the IL-23 signal during psoriasis is unknown. This study found that IL-23 is highly expressed in the epidermis of psoriasis lesions and positively correlated with histological neutrophil infiltration and clinical psoriasis area and severity index (PASI) scores. Furthermore, ART inhibits the migration and cell cycle, as well as tumor necrosis factor-alpha (TNF-α)-induced IL-23 expression in HaCaT cells in a dose-dependent manner, probably through interference with the nuclear factor kappa B (NF-κB) signalling pathway. Animal experiments in imiquimod (IMQ)-induced psoriasis-like mice model also suggested that ART dose-dependently reduces IL-23 in the epidermis and ameliorates neutrophil infiltration. These findings thus provide further molecular evidence supporting ART as a promising drug for psoriasis in clinic.
青蒿琥酯(ART)是一种具有多功能免疫调节作用的抗疟药物,可减轻银屑病病情。ART可减轻小鼠的银屑病样皮炎,但对血液中的促炎细胞因子无影响。因此,我们推测皮肤可能是ART治疗银屑病时的靶组织。白细胞介素(IL)-23/IL-17轴在银屑病发病机制中起关键作用。然而,ART在银屑病过程中是否以及如何调控IL-23信号尚不清楚。本研究发现,IL-23在银屑病皮损表皮中高表达,且与组织学上的中性粒细胞浸润以及临床银屑病面积和严重程度指数(PASI)评分呈正相关。此外,ART以剂量依赖的方式抑制HaCaT细胞的迁移和细胞周期,以及肿瘤坏死因子-α(TNF-α)诱导的IL-23表达,这可能是通过干扰核因子κB(NF-κB)信号通路实现的。在咪喹莫特(IMQ)诱导的银屑病样小鼠模型中的动物实验也表明,ART可剂量依赖性地降低表皮中的IL-23水平,并改善中性粒细胞浸润。因此,这些发现提供了进一步的分子证据,支持ART作为临床上治疗银屑病的一种有前景的药物。