Yang Jing, Chi Xiang, Zhang Jing, Zheng Li, Deng Liehua, Zhang Xin
Department of Dermatology, The First Affiliated Hospital of Jinan University and Jinan University Institute of Dermatology, Guangzhou 510630 Guangdong, PR China; Department of Dermatology, Foshan Women and Children Hospital, Foshan 528000 Guangdong, PR China.
Department of Dermatology, Foshan Women and Children Hospital, Foshan 528000 Guangdong, PR China.
Gene. 2025 Sep 10;964:149633. doi: 10.1016/j.gene.2025.149633. Epub 2025 Jun 14.
Our study attempted to explore the potential treatment of thiolutin (THL), a newly confirmed NLRP3 inhibitor, on atopic dermatitis (AD). The AD model was constructed on BALB/c mice using 2,4-Dinitrochlorobenzene (DNCB). THL treatment (2.5 or 10 mg/kg, every 2 days) was began on Day 7. The ear swelling and body weight of mice were monitored every three days. On day 21, after recording the scratching behaviors of each mouse, blood and skin samples were harvested to analyze serum IgE level and inflammatory cytokine production, epidermal thickness, mast cell infiltration, as well as the expression of NLRP3 inflammasome-related markers of lesional skin. THL administration attenuates AD-like symptoms stimulated by DNCB in mice, as evidenced by the quantified ear swelling, skin lesion, and scratching behaviors. THL decreased the systemic IgE level and the production of IL-5 and IL-4 in the lesional ear skin of the AD model mice. DNCB-induced epidermal thickening and lesional mast cell infiltration were reduced by THL. THL significantly suppressed the DNCB-induced upregulation of NLRP3, ASC, and Caspase-1 in lesional skin. Once NLRP3 was knocked out, the protection of THL against AD was diminished. THL can protect against experimental AD by blocking NLRP3 inflammasome activation. Our findings make THL a potentially therapeutic agent for AD.
我们的研究试图探索新确认的NLRP3抑制剂硫藤黄素（THL）对特应性皮炎（AD）的潜在治疗作用。使用2,4-二硝基氯苯（DNCB）在BALB/c小鼠上构建AD模型。在第7天开始进行THL治疗（2.5或10mg/kg，每2天一次）。每三天监测小鼠的耳部肿胀和体重。在第21天，记录每只小鼠的抓挠行为后，采集血液和皮肤样本，以分析血清IgE水平、炎性细胞因子产生、表皮厚度、肥大细胞浸润以及皮损处皮肤NLRP3炎性小体相关标志物的表达。THL给药减轻了DNCB刺激的小鼠AD样症状，量化的耳部肿胀、皮肤损伤和抓挠行为证明了这一点。THL降低了AD模型小鼠皮损耳部皮肤的全身IgE水平以及IL-5和IL-4的产生。THL减少了DNCB诱导的表皮增厚和皮损处肥大细胞浸润。THL显著抑制了DNCB诱导的皮损处皮肤中NLRP3、ASC和半胱天冬酶-1的上调。一旦NLRP3被敲除，THL对AD的保护作用就会减弱。THL可通过阻断NLRP3炎性小体激活来预防实验性AD。我们的研究结果使THL成为AD的一种潜在治疗药物。
